Hypertonic salt solution for peri-operative fluid management

  • Review
  • Intervention

Authors


Abstract

Background

Fluid excess may place people undergoing surgery at risk for various complications. Hypertonic salt solution (HS) maintains intravascular volume with less intravenous fluid than isotonic salt (IS) solutions, but may increase serum sodium. This review was published in 2010 and updated in 2016.

Objectives

To determine the benefits and harms of HS versus IS solutions administered for fluid resuscitation to people undergoing surgery.

Search methods

In this updated review we have searched the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2016); MEDLINE (January 1966 to April 2016); EMBASE (January 1980 to April 2016); LILACS (January 1982 to April 2016) and CINAHL (January 1982 to April 2016) without language restrictions. We conducted the original search on April 30th, 2007, and reran it on April 8th, 2016.

Selection criteria

We have included randomized clinical trials (RCTs) comparing HS to IS in people undergoing surgery, irrespective of blinding, language, and publication status.

Data collection and analysis

Two independent review authors read studies that met our selection criteria. We collected study information and data using a data collection sheet with predefined parameters. We have assessed the impact of HS administration on mortality, organ failure, fluid balance, serum sodium, serum osmolarity, diuresis and physiologic measures of cardiovascular function. We have pooled the data using the mean difference (MD) for continuous outcomes. We evaluated heterogeneity between studies by I² percentage. We consider studies with an I² of 0% to 30% to have no or little heterogeneity, 30% to 60% as having moderate heterogeneity, and more than 60% as having high heterogeneity. In studies with low heterogeneity we have used a fixed-effect model, and a random-effects model for studies with moderate to high heterogeneity.

Main results

We have included 18 studies with 1087 participants of whom 545 received HS compared to 542 who received IS. All participants were over 18 years of age and all trials excluded high-risk patients (ASA IV). All trials assessed haematological parameters peri-operatively and up to three days post-operatively.

There were three (< 1%) deaths reported in the IS group and four (< 1%) in the HS group, as assessed at 90 days in one study. There were no reports of serious adverse events. Most participants were in a positive fluid balance postoperatively (4.4 L IS and 2.5 L HS), with the excess significantly less in HS participants (MD -1.92 L, 95% confidence interval (CI) -2.61 to -1.22 L; P < 0.00001). IS participants received a mean volume of 2.4 L and HS participants received 1.49 L, significantly less fluid than IS-treated participants (MD -0.91 L, 95% CI -1.24 to -0.59 L; P < 0.00001). The maximum average serum sodium ranged between 138.5 and 159 in HS groups compared to between 136 and 143 meq/L in the IS groups. The maximum serum sodium was significantly higher in HS participants (MD 7.73, 95% CI 5.84 to 9.62; P < 0.00001), although the level remained within normal limits (136 to 146 meq/L).

A high degree of heterogeneity appeared to be related to considerable differences in the dose of HS between studies. The quality of the evidence for the outcomes reported ranged from high to very low. The risk of bias for many of the studies could not be determined for performance and detection bias, criteria that we assess as likely to impact the study outcomes.

Authors' conclusions

HS reduces the volume of intravenous fluid required to maintain people undergoing surgery but transiently increases serum sodium. It is not known if HS affects survival and morbidity, but this should be examined in randomized controlled trials that are designed and powered to test these outcomes.

Résumé scientifique

Solution saline hypertonique pour la gestion des fluides périopératoire

Contexte

L'excès de liquide peut impliquer un risque de complications diverses pour les personnes subissant une intervention chirurgicale. La solution saline hypertonique (SSH) maintient le volume intravasculaire avec moins de liquide intraveineux que les solutions salines isotoniques (SSI), mais peut augmenter la natrémie. Cette revue a été publiée en 2010 et mise à jour en 2016.

Objectifs

Déterminer les avantages et les inconvénients des solutions SSH versus SSI administrées pour la réanimation liquidienne des personnes subissant une intervention chirurgicale.

Stratégie de recherche documentaire

Dans cette revue mise à jour, nous avons effectué des recherches dans le registre Cochrane des essais contrôlés (CENTRAL, numéro 4, 2016) ; MEDLINE (de janvier 1966 à avril 2016) ; EMBASE (de janvier 1980 à avril 2016) ; LILACS (de janvier 1982 à avril 2016) et CINAHL (de janvier 1982 à avril 2016), sans restriction de langue. Nous avons effectué la recherche originale le 30 avril 2007, et elle a été réitérée le 8 avril 2016.

Critères de sélection

Nous avons inclus les essais cliniques randomisés (ECR) comparant la SSH à une SSI chez les personnes subissant une intervention chirurgicale, indépendamment de la mise en aveugle, la langue ou le statut de publication.

Recueil et analyse des données

Deux auteurs indépendants de la revue ont lu les études qui répondaient à nos critères de sélection. Nous avons recueilli les informations et les données d'étude à l'aide d'un formulaire de collecte de données avec des paramètres prédéfinis. Nous avons évalué l'impact de l'administration d'une SSH sur la mortalité, la défaillance d'organes, l'équilibre des liquides, la natrémie, l'osmolarité sérique, la diurèse et sur les mesures physiologiques de la fonction cardiovasculaire. Nous avons regroupé les données à l'aide de la différence moyenne (DM) pour les résultats continus. Nous avons évalué l'hétérogénéité entre les études par le pourcentage I². Nous avons considéré les études avec un I² de 0 % à 30 % comme ayant peu ou pas d'hétérogénéité, de 30 % à 60 % comme présentant une hétérogénéité modérée, et de plus de 60 % comme présentant une hétérogénéité élevée. Pour les études avec une hétérogénéité faible, nous avons utilisé un modèle à effets fixes et un modèle à effets aléatoires pour les études présentant une hétérogénéité modérée à élevée.

Résultats principaux

Nous avons inclus 18 études avec 1087 participants, dont 545 ont bénéficié d'une SSH par rapport à 542 ayant reçu une SSI. Tous les participants étaient âgés de plus de 18 ans et tous les essais ont exclu les patients à hauts risques (ASA IV). Tous les essais évaluaient les paramètres hématologiques en péri-opératoire et jusqu'à trois jours après l'opération.

Il y a eu trois décès rapportés dans le groupe SSI (<  1 %) et quatre dans le groupe SSH (<  1 %), évalués à 90 jours dans une étude. Aucun événement indésirable grave n'a été rapporté. La plupart des participants avaient un bilan hydrique post-opératoire positif (4,4 l SSI et 2,5 l SSH), avec un excès significativement inférieure parmi les participants SSH (DM -1,92 l, intervalle de confiance (IC) à 95 % -2,61 à -1,22 l ; P < 0,00001). Les participants SSI ont reçu un volume moyen de 2,4 l et les participants SSH ont reçu 1,49 l, significativement moins de liquide que les participants traités par SSI (DM -0,91 l, IC à 95 % -1,24 à -0,59 l ; P < 0,00001). Le taux moyen maximum de sodium sérique était compris entre 138,5 et 159 dans les groupes SSH par rapport aux groupes SSI dont le taux était compris entre 136 et 143 mEq/l. Le taux maximum de sodium sérique était significativement plus élevé chez les participants SSH (DM 7,73, IC à 95 % 5,84 à 9,62 ; P < 0,00001), bien que son niveau soit resté dans les limites normales (de 136 à 146 mEq/l).

Un degré élevé d'hétérogénéité semblait être associé à des différences considérables au niveau de la dose de SSH entre les études. La qualité des preuves des résultats rapportés varie d'élevée à très faible. Pour un grand nombre de ces études, le risque de biais n'a pas pu être déterminé pour ce qui est des biais de performance et de détection, critères que nous considérons comme susceptibles d'avoir un impact sur les résultats de l'étude.

Conclusions des auteurs

La SSH réduit le volume de liquide intraveineux nécessaire pour maintenir les personnes subissant une intervention chirurgicale, mais augmente de façon transitoire la natrémie. On ignore si la SSH affecte la survie et la morbidité, question qui devrait être examinée dans des essais contrôlés randomisés qui sont conçus et dotés de la puissance nécessaire pour tester ces critères de jugement.

Resumo

Solução salina hipertônica para o manejo de fluidos no perioperatório

Introdução

O excesso de fluido pode fazer com que pessoas submetidas a cirurgias estejam expostas a várias complicações. Solução salina hipertônica (SH) mantém o volume intravascular com menos fluido intravenoso do que soluções salinas isotônicas (SI), mas podem aumentar o sódio sérico. Esta revisão foi publicada em 2010 e atualizada em 2016.

Objetivos

Determinar os benefícios e prejuízos de soluções SH versus SI administradas para ressuscitação de pessoas submetidas a cirurgia.

Métodos de busca

Nesta revisão atualizada nós buscamos no Cochrane Central Register of Controlled Trials (CENTRAL; Edição 4, 2016); MEDLINE (Janeiro de 1966 a Abril de 2016); EMBASE (Janeiro de 1980 a Abril de 2016); LILACS (Janeiro de 1982 a Abril de 2016) e CINAHL (Janeiro de 1982 a Abril de 2016) sem restrições de idioma. Nós conduzidos a busca original em 30 de Abril de 2007 e repetimos em 8 de Abril de 2016.

Critério de seleção

Incluímos ensaios clínicos randomizados (ECRs) comparando SH a SI em pessoas submetidas a cirurgia, independente do cegamento, idioma, e estado de publicação.

Coleta dos dados e análises

Dois revisores independentes leram os estudos que preencheram nosso critério de seleção. Nós coletamos informações do estudo e dados usando um formulário de coleta de dados com parâmetros pré definidos. Nós avaliamos o impacto da administração de SH em mortalidade, falência de órgãos, balanço de fluidos, sódio sérico, osmolaridade sérica, diurese e medidas fisiológicas da função cardiovascular. Nós agrupamos os dados usando a diferença da média (DM) para desfechos contínuos. Nós avaliamos heterogeneidade entre os estudos pela percentagem I². Nós consideramos estudos com um I² de 0% a 30% tendo pouca ou nenhuma heterogeneidade, 30% a 60% como tendo heterogeneidade moderada, e mais do que 60% como tendo alta heterogeneidade. Nos estudos com baixa heterogeneidade nós usamos um modelo de efeito fixo, e modelo de efeito ao acaso para estudos com moderada a alta heterogeneidade.

Principais resultados

Nós incluimos 18 estudos com 1087 participantes dos quais 545 receberam SH comparado com 542, que receberam SI. Todos os participantes tinham mais que 18 anos de idade e todos os ensaios clínicos excluíram pacientes de alto risco (ASA IV). Todos os ensaios clínicos avaliaram parâmetros hematológicos no peri-operatório e até três dias do pós-operaratório.

Houve três mortes (<1%) relatadas no grupo SI e quatro (<1%) no grupo SH, que foi avaliado em 90 dias em um estudo. Não houve relato de eventos adversos graves. A maioria dos participantes apresentaram balanço de fluidos positivo no pós-operatório (4,4L SI e 2,5L SH), com excesso significantemente menor no grupo SH (DM -1,92 L, 95% intervalo de confiança (IC) -2,61 a -1,22 L; P < 0.00001). Participantes do grupo SI receberam um volume médio de 2,4L e os SH, receberam 1,49L, significantemente menos fluido do que o grupo tratado com SI (DM -0,91 L, IC 95% -1,24 a -0,59 L; P < 0.00001). A média máxima de sódio sérico variou entre 138,5 e 159 no grupo SH comparado com a variação entre 136 e 143 mEq/L no grupo SI. A média de sódio sérico foi significantemente maior no grupo SH (DM 7,73, IC 95% 5,84 a 9,62; P < 0.00001), embora o nível tenha permanecido dentro dos limites normais (136 a 146 meq/L).

Um alto grau de heterogeneidade parecia estar relacionado a diferenças consideráveis na dose de SH entre os estudos. A qualidade da evidência para os desfechos relatados variaram de alto a muito baixo. O risco de viés para a maioria dos estudos não pode ser determinado para a performance e detecção de vies, critério que nós acessamos como prováveis de interferir nos desfechos dos estudos.

Conclusão dos autores

SH reduziu o volume de fluido intravenoso necessário para manter pessoas submetidas a cirurgias mas provocou aumento transitório do sódio sérico. Não é sabido se SH afeta a sobrevida e morbidade, mas isto deveria ser examinado em ensaios clínicos controlados randomizados que sejam desenhados e reforçados para testar estes resultados.

Plain language summary

Increased salt in solution to maintain fluid during surgery

Review question

Are solutions containing more salt than is normally used safe during surgery?

Background

People usually require fluids during surgery. Sometimes large volumes of fluid are given in order to maintain adequate blood volume, but these volumes may leave people with too much fluid. The fluids normally used during surgery have a salt balance similar to that found in blood, and are called isotonic. Hypertonic salt solutions (HS) have a higher sodium concentration than isotonic salt solutions (IS). HS might benefit people undergoing surgery by reducing the total volume of fluid required.

Search date

The evidence is up to date to April 8th, 2016.

Study characteristics

We included 18 trials that compared HS to IS in people undergoing surgery. The trials included 1087 participants. Five hundred and forty-five (545) participants received HS and 542 received IS during their operations. The participants were randomly assigned to their groups. The studies took place in 11 countries. Study participants were over the age of 18. All studies excluded people with serious health risks from participating. All studies monitored fluid levels during the operation and up to three days after.

Key results

There were seven deaths in total, three (less than 1%) from the IS group and four (less than 1%) from the HS group. The risk of death was very low in these studies. The studies did not report the occurrence of serious adverse events.

Thirteen studies reported the amount of fluid given. The IS group received a mean of 2.4 L and the HS group received 0.91 L less (1.49 L). The highest amount of sodium in the blood over the course of the study was reported by 16 studies. The IS group had a median of 139 meq/L and the HS group was 7.73 meq/L higher. The normal acceptable range is 136 to 146 meq/L.

Quality of the evidence

For deaths and adverse events the trials lacked sufficient size and duration to adequately assess differences. We assessed the quality of evidence for deaths to be very low, and future studies are likely to change the result reported here.

The reporting of the highest amount of sodium is of moderate quality. The measuring of blood sodium during an operation is a common measurement that is unlikely to be misrepresented.

Résumé simplifié

Solution saline au taux de sel augmenté afin de maintenir l'équilibre hydrique pendant l'intervention chirurgicale

Question de la revue

Les solutions contenant plus de sel que la dose habituelle peuvent-elles être utilisées de façon sûre pendant une intervention chirurgicale  ?

Contexte

Les patients ont généralement besoin de liquides pendant une intervention chirurgicale. De grands volumes de liquides sont parfois administrés afin de maintenir le volume sanguin adéquate, mais ces volumes peuvent laisser trop de liquides chez certaines personnes. Les liquides normalement utilisés pendant une opération ont un taux de sel similaire à celui du sang, et sont appelés isotoniques. Les solutions salines hypertoniques (SSH) ont une concentration en sodium plus élevée que les solutions salines isotoniques (SSI). La SSH pourrait être bénéfique aux patients subissant une opération chirurgicale en réduisant le volume total de liquide nécessaire.

Date de la recherche

Les preuves sont à jour jusqu'au 8 avril 2016.

Caractéristiques de l'étude

Nous avons inclus 18 essais qui comparaient une SSH à une SSI chez les patients subissant une intervention chirurgicale. Les essais comptaient 1087 participants. Cinq cent quarante-cinq (545) participants ont reçu une SSH et 542 ont reçu une SSI pendant leur opération. Les participants ont été placés au hasard dans leurs groupes. L'étude a été menée dans 11 pays. Les participants étaient âgés de plus de 18 ans. Toutes les études ont exclu les personnes dont la participation impliquait des risques graves pour la santé. Toutes les études ont surveillé les niveaux des fluides au cours de l'opération et jusqu'à trois jours après.

Principaux résultats

Il y a eu sept décès au total, trois dans le groupe SSI (moins de 1 %) et quatre dans le groupe SSH (moins de 1 %). Le risque de décès était très faible dans ces études. Les études n'ont pas rendu compte d'événements indésirables graves.

Treize études ont rendu compte de la quantité de liquide donné. Le groupe SSI a reçu en moyenne 2,4  l et le groupe SSH a reçu 0,91 l de moins (1,49 l). La plus grande quantité de sodium dans le sang au cours de l'étude a été rapportée dans 16 études. Le groupe SSI présentait une médiane de 139 mEq/l ; la médiane du groupe SSH était de 7,73 mEq/l plus élevée. La fourchette normale acceptable est de 136 à 146 mEq/l.

Qualité des preuves

En ce qui concerne les décès et événements indésirables, les études auraient gagné à être plus importantes et plus longues afin d'évaluer les différences de façon adéquate. La qualité des preuves concernant les décès a été évaluée comme très faible, et les études futures sont susceptibles de modifier les résultats rapportés ici.

La consignation de la plus grande quantité de sodium est de qualité modérée. La mesure de sodium dans le sang pendant une opération est une mesure courante qui a peu de chances d'être déformée.

Notes de traduction

Post-édition : Marie Becquet (M2 ILTS, Université Paris Diderot)

Laienverständliche Zusammenfassung

Höher konzentrierte Salzlösungen zur Stabilisation des Flüssigkeitshaushalt während Operationen

Review-Frage

Ist die Anwendung von Lösungen mit höherem Salzgehalt als gewöhnlich bei Operationen verträglich?

Hintergrund

Menschen brauchen während Operationen normalerweise Flüssigkeitszufuhr. Manchmal werden große Mengen an Flüssigkeit verabreicht um ein angemessenes Blutvolumen stabil zu halten, was jedoch auch zu einer Überwässerung führen könnte. Die Flüssigkeiten, die normalerweise während Operationen verwendet werden, haben einen Salzgehalt der dem des Blutes entspricht. Man nennt sie isotonisch. Hypertonische Salzlösungen (HS) haben eine höhere Konzentration an Natrium als isotonische Salzlösungen (IS). HS könnten für Menschen während einer Operation nützlich sein, weil sie die Menge an insgesamt benötigter Flüssigkeit reduzieren.

Datum der Suche

Die Evidenz ist auf dem Stand vom 8. April 2016.

Studienmerkmale

Wir schlossen 18 Studien ein, in denen die Verwendung von HS und IS bei Menschen während einer Operation verglichen wurde. Die Studien schlossen 1087 Teilnehmer ein. 545 Teilnehmer erhielten während ihrer Operation HS und 542 erhielten IS. Die Teilnehmer wurden ihren Gruppen zufällig zugeteilt. Die Studien fanden in 11 Ländern statt. Die Studienteilnehmer waren über 18 Jahre alt. Menschen mit schweren Gesundheitsrisiken wurden in keiner der Studien eingeschlossen. In allen Studien wurde der Flüssigkeitshaushalt während und bis zu drei Tage nach der Operation überwacht.

Hauptergebnisse

Insgesamt gab es sieben Todesfälle, drei (unter 1%) in der IS-Gruppe und vier (unter 1%) in der HS-Gruppe. Das Sterberisiko lag in den Studien sehr niedrig. Von schweren unerwünschten Ereignissen wurde in den Studien nicht berichtet.

In dreizehn Studien wurde die Menge an verabreichter Flüssigkeit angegeben. Die IS-Gruppe erhielt durchschnittlich 2,4 L, die HS-Gruppe durchschnittlich 0,91 L weniger (1,49 L). In 16 Studien wurde die höchste, während der Studie gemessene Natriumkonzentration im Blut angegeben. Die IS-Gruppe hatte im Mittel (Median) 139 mval/L Natrium im Blut, die HS-Gruppe 7,73 mval/L mehr. Der Normbereich liegt zwischen 136 und 146 mval/L. (Anm. d. Red.: 1 val entpricht 1 Mol * Elementarladungen, hier entspricht 1 mval/L=mmol/L)

Qualität der Evidenz

Um Unterschiede bezüglich der Todesfälle und der unerwünschten Ereignisse zu ermitteln, waren die Studien nicht groß und nicht lange genug angelegt. Die Qualität der Evidenz für Todesfälle schätzen wir als sehr niedrig ein. Zukünftige Studien werden die hier berichteten Ergebnisse wahrscheinlich beeinflussen.

Die Berichterstattung über die höchsten Natriumkonzentrationen sind von moderater Qualität. Die Bestimmung der Natriumkonzentration im Blut während einer Operation ist eine gängige Messung bei der es unwahrscheinlich ist, dass sie falsche Ergebnisse liefert.

Anmerkungen zur Übersetzung

V. Labonté, freigegeben durch Cochrane Deutschland.

Streszczenie prostym językiem

Stosowanie roztworów soli o większym stężeniu w celu utrzymania odpowiedniej ilości płynów podczas zabiegu operacyjnego

Pytanie przeglądu

Czy stosowanie podczas zabiegu operacyjnego roztworów, które zawierają więcej soli niż standardowo jest bezpieczne?

Wprowadzenie

Zazwyczaj podczas zabiegu operacyjnego konieczne jest podawanie pacjentowi płynów. Czasami duże objętości płynów podaje się w celu utrzymania odpowiedniej objętości krwi, jednak może się to wiązać ze zbyt dużą objętością płynów pozostałych w organizmie. Płyny, których zwykle używa się podczas operacji charakteryzuje stężenie soli zbliżone do tego występującego we krwi i nazywa się je izotonicznymi. Hipertoniczne roztwory soli zawierają większe stężenie sodu niż roztwory izotoniczne. Stosowanie roztworów hipertonicznych soli może przynieść korzyści u osób poddawanych zabiegom operacyjnym poprzez zmniejszenie całkowitej objętości podawanych płynów.

Data wyszukiwania

Dane naukowe są aktualne do 8 kwietnia 2016 roku.

Charakterystyka badania

Włączyliśmy 18 badań, w których porównywano stosowanie hipertonicznych roztworów soli i roztworów izotonicznych u osób poddawanych zabiegom operacyjnym. Do badań włączono 1087 uczestników. Podczas zabiegu operacyjnego 545 uczestników otrzymało hipertoniczny roztwór soli, a 542 roztwór izotoniczny. Uczestników przydzielono do grup losowo. Badania przeprowadzono w 11 krajach. Uczestnicy badań byli w wieku >18 lat. Z udziału we wszystkich badaniach wykluczono osoby, u których uczestnictwo w badaniu wiązało się z dużym ryzykiem dla zdrowia. We wszystkich badaniach poziom płynów monitorowano podczas zabiegu operacyjnego oraz do 3 dni po nim.

Główne wyniki

Łącznie odnotowano 7 zgonów: 3 zgony (<1%) w grupie pacjentów, którzy otrzymali podczas zabiegu izotoniczny roztwór soli oraz 4 zgony (<1%) w grupie pacjentów, którzy otrzymali hipertoniczny roztwór soli. Ryzyko zgonu w tych badaniach było bardzo małe. W badaniach nie podano informacji na temat częstości występowania poważnych objawów niepożądanych.

W 13 badaniach podano jaką ilość płynów otrzymali pacjenci. Osoby w grupie izotonicznego roztworu soli otrzymały średnio 2,4 l tego roztworu, podczas gdy pacjenci w grupie hipertonicznego roztworu soli otrzymali go o 0,91 l mniej (1,49 l). Informację na temat największego odnotowanego w przebiegu leczenia stężenia sodu we krwi podano w 16 badaniach. W grupie, która otrzymała izotoniczny roztwór soli wynosiło ono 139 mEq/l (mediana), a w grupie hipertonicznego roztworu soli było ono o 7,73 mEq/l większe. Zakres dopuszczalnych stężeń wynosi od 136 do 146 mEq/l.

Jakość danych naukowych

Dla ryzyka zgonu oraz objawów niepożądanych w badaniach brakowało odpowiedniej liczby uczestników badania oraz odpowiedniej długości okresu obserwacji, żeby móc właściwie ocenić różnice. Jakość danych naukowych dla zgonów oceniliśmy jako bardzo niską. Przyszłe badania prawdopodobnie zmienią podane w tym przeglądzie wyniki.

Jakość danych naukowych dla odnotowanego największego stężenia sodu we krwi jest umiarkowana. Pomiar stężenia sodu we krwi podczas zabiegu operacyjnego jest powszechnie wykonywanym pomiarem, dlatego jest mało prawdopodobne aby został źle wykonany.

Uwagi do tłumaczenia

Tłumaczenie: Piotr Małczak Redakcja: Karolina Moćko

Laički sažetak

Otopina s povećanom količinom soli za održavanje razine tekućine tijekom operacije

Istraživačko pitanje

U ovom Cochrane sustavnom pregledu literature analizirani su klinički pokusi u kojma je istraženo jesu li otopine koje sadrže više soli od onih koje se normalno koriste, sigurne za primjenu tijekom operacije.

Dosadašnje spoznaje

Ljudima obično treba dati tekućinu tijekom operacije. Ponekad se daju velike količine tekućine kako bi se zadržao odgovarajući volumen krvi, međutim, to može dovesti do zadržavanja tih prevelikih količina tekućine u organizmu. Tekućine koje se obično riste za vrijeme operacije imaju ravnotežu soli sličnu onoj u krvi i nazivaju se izotoničnim otopinama. Hipertonične otopine soli (engl. hypertonic salt solutions, HS) imaju veću koncentraciju natrija od izotoničnih otopina (engl. isotonic salt solutions, IS). HS bi mogle biti korisne tijekom operacije jer smanjuju ukupni volumen potrebne tekućine.

Datum pretraživanja literature

Dokazi se odnose na literaturu objavljenu do 8. travnja 2016.

Obilježja uključenih istraživanja

Uključili smo 18 ispitivanja koja su uspoređivala primjenu HS i IS kod ljudi koji su bili podvrgnuti operaciji. Ta su ispitivanja ukupno uključivala 1087 sudionika. Pet stotina četrdeset i pet (545) sudionika je primilo HS i 542 je primilo IS tijekom operacija. Sudionici su nasumice podijeljeni u skupine. Ispitivanja su se provodila u 11 zemalja. Sudionici ispitivanja su bili stariji od 18 godina. Sve su studije isključile osobe kod kojih bi sudjelovanje u istraživanju moglo uzrokovati ozbiljne rizike za njihovo zdravlje. Sve su studije pratile razine tekućine tijekom operacije i do tri dana poslije.

Ključni rezultati

Zabilježeno je ukupno sedam smrtnih slučajeva, tri (manje od 1%) u IS skupini i četiri (manje od 1%) u HS skupini. Rizik od smrti je bio vrlo nizak u ovim studijama. Studije nisu opisale pojavu ozbiljnih nuspojava.

Trinaest studija je prikazalo podatke o količini tekućine koja je primijenjena. IS skupina je dobila srednju vrijednost od 2,4 L tekućine, dok je HS skupina primila 0,91 L manje (1,49 L). Ukupno 16 studija je prikazalo podatke o najvećoj količini natrija u krvi tijekom trajanja ispitivanja. IS skupina je imala medijan količine natrija 139 meg/L, dok je HS skupina bila za 7,73 meq/L veća. Normalan prihvatljiv raspon je između 136 do 146 meq/L.

Kvaliteta dokaza

Za podatke o smrti i nuspojavama ispitivanja su bila nedovoljne veličine i trajanja da bi se na odgovarajući način procijenila razlika. Procijenili smo da je kvaliteta dokaza za smrt vrlo niska, a buduće studije će vjerojatno promijeniti rezultate koji su ovdje izneseni.

Prikazivanje podataka o najvišoj količini natrija je umjerene kvalitete. Mjerenje natrija u krvi tijekom operacije je često mjerenje koje vjerojatno nije krivo predstavljeno.

Bilješke prijevoda

Hrvatski Cochrane
Prevela: Jasna Safić
Ovaj sažetak preveden je u okviru volonterskog projekta prevođenja Cochrane sažetaka. Uključite se u projekt i pomozite nam u prevođenju brojnih preostalih Cochrane sažetaka koji su još uvijek dostupni samo na engleskom jeziku. Kontakt: cochrane_croatia@mefst.hr

Resumo para leigos

Acrescentar sódio na solução para manutenção de fluidos durante a cirurgia

Pergunta da revisão

Soluções que contem mais sódio do que o normal são seguras durante a cirurgia?

Introdução

Pessoas geramente requerem fluidos durante a cirurgia. Ás vezes, grande volumes de fluidos são administrados para manter um volume sanguíneo adequado, mas estes volumes podem deixar as pessoas com excesso de fluidos. Os fluidos geralmente usados durante cirurgia tem balanço salino similar ao encontrado no sangue, e por isso, são chamados de isotônicos. Soluções salinas hipertônicas (SH) tem maior concentração de sódio do que as soluções isotônicas (SI). SH podem beneficiar pessoas submetidas à cirurgia pela redução do volume total de fluido necessário.

Data da pesquisa

A evidência é atual até 8 de Abril de 2016.

Caracterísiticas do estudo

Nós incluimos 18 ensaios clínicos que compararam SH a SI em indivíduos submetidos a cirurgia Os ensaios clínicos incluiram 1087 participantes. Quinhentos e quarenta e cinco (545) participantes receberam SH e 542 receberam SI durante suas cirurgias. Os participantes foram randomicamente distribuídos em seus grupos. Os estudos foram realizados em 11 países. Participantes do estudo tinham mais que 18 anos de idade. Todos os estudos excluíram pessoas que possuíam sério risco de saúde a sua participação. Todos os estudos monitoraram os níveis de fluído durante a cirurgia e até 3 dias após.

Resultados chave

Houve sete mortes no total, três (menos que 1%) foram do grupo SI e quatro (menos que 1%) foram do grupo SH. O risco de morte foi muito baixo nestes estudos. Os estudos não reportaram ocorrência de eventos adversos graves.

Treze estudos relataram a quantidade de fluido administrado. O grupo SI recebeu uma média de 2,4L e o grupo SH recebeu 0,91L a menos (1,49 L). Maior quantidade de sódio sérico durante o curso do estudo foi relatado por 16 estudos O grupo SI teve uma mediana de 139mEq/L e no grupo SH foi 7,73mEq/L maior. O faixa normal aceitável é de 136 a 146 mEq/L.

Qualidade da evidência

Para mortes e eventos adversos, os ensaios clínicos carecem de tamanho suficiente e duração para estabelecer diferenças adequadamente. Nós consideramos que a qualidade de evidência para mortes é muito baixa, e mais estudos são necessários para mudar os resultados aqui relatados.

O relato de alta quantidade de sódio é de moderada qualidade. A mensuração de sódio sérico durante uma cirurgia é uma medição comum que é improvável de ser mal interpretada.

Notas de tradução

Tradução da Unidade de Medicina Baseada em Evidências da Unesp, Brazil (Marcelo Tabary de Oliveira Carlucci) Contato: portuguese.ebm.unit@gmail.com Translation notes: CD005576

Summary of findings(Explanation)

Summary of findings for the main comparison. Hypertonic salt compared to isotonic salt solution for peri-operative resuscitation
  1. 1Downgraded (2 levels) for indirectness: The majority of studies have an insufficient follow-up period to adequately measure the outcome.
    2Downgraded (1 level) for publication bias: Only one study contributes explicit evidence for the outcome.
    3Downgraded (1 level) for risk of bias: The majority of the studies have not confirmed blinding of outcome assessors; bias could seriously impact this result.
    4Downgraded (1 level) for imprecision: The volume of crystalloid solution delivered between studies has a large range.
    5Downgraded (1 level) for imprecision: The duration of sample collection varies widely from study to study.

Hypertonic salt compared to isotonic salt solution for peri-operative resuscitation
Patient or population: any people undergoing surgery with fluid resuscitation
Settings: people undergoing non-emergency surgery that requires fluid resuscitation in a hospital operating room in;Brazil, China,Denmark, Finland, France, Germany, Indonesia, Japan, Lebanon, Niger, USA.
Intervention: hypertonic salt solution
Comparison: isotonic salt solution
OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments
Assumed riskCorresponding risk
isotonic salt solution for peri-operativeresuscitation Hypertonic salt

Mortality

Follow-up: range 1 to 90 days

Study population-1087
(18 RCTs)
⊕⊝⊝⊝
VERY LOW1,2
Any recorded death during the study period. The risk of bias impacting this outcome is considered to be low. Only one study had incidents of mortality
--

Serious adverse events

Follow-up: range 1 to 90 days

---

1087

(18 RCTs)

⊕⊝⊝⊝
VERY LOW1,2
Other adverse outcomes are collected as defined by each trial or if any of the following occurred: any organ failure, including renal, pulmonary, cardiac, or cerebral

Fluid balance (L)

Follow-up: range 1 to 3 days

The mean fluid balance (L) was 4.375The mean fluid balance (L) in the intervention group was 1.92 lower (2.61 lower to 1.22 lower)-737
(8 RCTs)
⊕⊕⊝⊝
LOW 3,4
The change in participant fluid volume at the end of fluid administration. A neutral fluid balance would be optimal

Total volume of crystalloid administered (L)

Follow-up: range 1 to 3 days

The mean total volume of crystalloid administered (L) was 2.43The mean total volume of crystalloid administered (L) in the intervention group was 0.91 lower (1.24 lower to 0.59 lower)-871
(13 RCTs)
⊕⊕⊕⊝
MODERATE4
The total volume of fluid delivered intravenously over the study period. There are no defined minimum or maximum values for fluid delivery during surgery. Less resuscitating fluid is preferred

Peak serum sodium

Follow-up: range 1 to 3 days

The mean peak serum sodium (meq/L) was 139.1The mean peak serum sodium (meq/L) in the intervention group was 7.73 higher (5.84 higher to 9.62 higher)-780
(16 RCTs)
⊕⊕⊕⊝
MODERATE5
The measurement of this variable is a common practice in operative procedures. Measured as the peak amount of sodium in the blood, given in milliequivelants per litre, over the study period. The normal acceptable range is 136 to 146 meq/L

Final serum sodium

Follow-up: range 1 to 3 days

The mean final serum sodium (meq/L) was 138.3The mean final serum sodium (meq/L) in the intervention group was 3.45 higher (2.46 higher to 4.44 higher)-640
(12 RCTs)
⊕⊕⊕⊝
MODERATE5
The measurement of this variable is common practice in operative procedures. Measured as the final amount of sodium in the blood, given in milliequivelants per litre, at the end of the study. The normal acceptable range is 136 to 146 meq/L

Maximum intraoperative cardiac index

Follow-up: 1 to 3 days

The mean maximum intraoperative cardiac index (L/min/M²) was 2.9The mean maximum intraoperative cardiac index (L/min/m²) in the intervention group was 0.34 higher (0.19 higher to 0.49 higher)-418
(6 RCTs)
⊕⊕⊕⊕
HIGH
The measurement of this variable is common practice in operative procedures. Measured by the volume of blood passing through one square meter each minute (L/min/M²). The normal range is 2.5 - 4.0 L/min/M²
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval;
GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

Background

Description of the condition

Low-volume resuscitation with hypertonic crystalloid solutions has been investigated for over 20 years (Shackford 1983). More recently, alterations in cellular immune function with hypertonic salt solution (HS) administration have been demonstrated in experimental and clinical studies (Kølsen-Petersen 2004; Rizoli 2006). Several randomized controlled trials (RCTs) of HS resuscitation in critically ill participants have been performed. A systematic review of HS compared to isotonic salt solution (IS) in resuscitation following burns or trauma was unable to reach a conclusion regarding benefit or harm in the presence of wide confidence intervals (Bunn 2004). Trials of HS alone, or in combination with colloids, have also been performed in the trauma population. A meta-analysis comparing 250 mL of HS (with or without dextran) with administration of 250 mL of isotonic crystalloid for the treatment of hypotension either in the field or at admission to the emergency department in 1233 trauma patients failed to demonstrate that HS with dextran confers a survival benefit (Wade 1997).

Description of the intervention

Standard peri-operative care includes IS administration to counter conditions which may cause transient intraoperative hypovolaemia including: fluid deprivation during preoperative fasting; vasodilatation due to epidural or general anaesthesia; third space sequestration of intravascular fluid; insensible fluid loss and intraoperative fluid or blood loss. These conditions are often reversed at the end of an operation. In fact, IS has been shown to increase the weight of people undergoing elective major surgery by an average of three to six kilograms (kg) (Grocott 2005). While most people tolerate the additional fluid well, postoperative improvement or reversal of the conditions outlined above may place those with compromised cardiovascular or renal function at increased risk for development of pulmonary oedema. People without cardiovascular or renal risk factors may also be adversely affected by peri-operative fluid gain. A recent RCT demonstrated that peri-operative fluid restriction resulted in fewer major or minor postoperative complications compared to traditional care in 172 adult participants undergoing elective colorectal surgery (Brandstrup 2003). Another study demonstrated that fluid overload delayed return of gastrointestinal function (Lobo 2002). Conversely, failure to maintain intravascular volume during surgery may place people at risk for cardiac or cerebral ischaemia. Indeed, supplemental peri-operative fluid administration has been shown to improve tissue oxygenation (Arkiliç 2003).

How the intervention might work

HS has the potential to reduce the total volume of fluid administered during operative procedures by allowing people to draw fluid from the interstitium (and other body compartments) to counter peri-operative hypotensive effects, and thereby provide Intravascular support without excess fluid administration. In situations where large volume resuscitation may be harmful, such as in brain trauma, a role for HS is emerging (Ogden 2005). Notwithstanding, several risks have been associated with HS, including potential hypernatraemia, metabolic acidosis and vasodilatation.

Why it is important to do this review

Several RCTs of prophylactic HS administration in the peri-operative period have been published. In contrast to other trials where HS has been combined with colloid solutions to treat hypotension, these RCTs may provide a clinical picture of the effect of HS on peri-operative fluid management.

Objectives

To determine the benefits and harms of HS versus IS solutions administered for fluid resuscitation to people undergoing surgery.

Methods

Criteria for considering studies for this review

Types of studies

We included RCTs comparing the administration of HS versus IS solution during non-emergency operative procedures, regardless of language or publication status. RCTs are the gold standard for comparing the effect of one treatment versus another.

Types of participants

We included all participants undergoing any surgical procedures.

Types of interventions

We have included peri-operative administration of either HS or IS solutions. We permitted concomitant measures so long as they applied to both arms of the study. We excluded studies that compared HS and a colloidal solution to IS alone. Additionally, we excluded studies that compared HS and IS solutions administered by inhalation or absorption from the nasal mucosa and involving non-surgical patient populations (burns, trauma and head injury).

Types of outcome measures

Primary outcomes
1. Mortality

Defined as any deaths occurring during the study period. Where all participants are included in the results for other outcomes we have extrapolated that as indicating no deaths.

2. Serious adverse events

We collected other adverse outcomes as defined by each trial, or if any of the following occurred: any organ failure, any requirement for dialysis (renal failure) or prolonged ventilation (pulmonary failure); use of medical therapy for either pulmonary oedema or circulatory support (cardiac failure) or for confusion (cerebral failure).

Secondary outcomes
3. Fluid balance over the study period

We used authors' definitions where provided. For studies not clearly specifying the study period, we defined it to include the immediate preoperative (induction of anaesthesia), intraoperative and postoperative periods (up to 24 hours after surgery). Studies can report the fluid balance by reporting the difference in fluid given minus fluid excreted or by the change in weight of the participant. For studies that only reported weight change, we applied a conversion factor, wherein 1 kg = 1 L (litre), to calculate fluid balance. Fluid balance is expressed in litres.

4. Total volume of intravenous fluid delivered

A report of the volume of resuscitating fluid given to the participant intravenously during the peri-operative and recovery period as reported by the studies. Fluid delivered is expressed in litres.

5. Peri-operative diuresis

A measure of the urine output from the participant during the operative period. Diuresis is reported as litres.

6. Maximum serum sodium concentration

As measured from the participant's blood during the study and reported as milliequivalents per litre (meq/L).

7. Final serum sodium concentration

As measured in the participant's blood at the end of follow-up, and reported as milliequivalents per litre (meq/L).

8. Duration of endotracheal intubation after operation

As reported by each study and converted to hours (h).

9. Duration of stay in intensive care after operation

As reported by each study and converted to hours (h).

10. Duration of stay in hospital after operation

As reported by each study and converted to days (d).

11. Other outcomes

We collected data regarding serum osmolarity, expressed as milliosmoles per kilogram of water (mOsm/kg H2O) and peri-operative haemodynamic parameters: pulmonary artery wedge pressure, measured by mm of mercury (mm Hg); and cardiac index (CI), derived from cardiac output (CO = Heart rate/stroke volume/1000) and body surface area (BSA), CI = CO/BSA; it is a measure of the volume of blood passing through one square meter each minute (L/min/M²).

Search methods for identification of studies

Electronic searches

For this updated review we have searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 4, 2016); MEDLINE (January 1966 to April 2016); EMBASE (January 1980 to April 2016); LILACS (January 1982 to April 2016) and CINAHL (January 1982 to April 2016). We limited the publication types to clinical trials, controlled clinical trials, RCTs, multicentre studies and meta-analyses, without language restrictions.

We originally used the search strategy described in the appendices (Appendix 1 MEDLINE; Appendix 2 EMBASE; Appendix 3 CINAHL; Appendix 4 LILACS; Appendix 5 CENTRAL) to search until August 2009. We have updated the search terms since the original search (see Appendix 6). In addition, we searched trial registries including clinicaltrials.gov/, www.controlled-trials.com/ and www.ifpma.org/clinicaltrials.html for ongoing trials. We sought letter or email contact with principal investigators to inform them of the meta-analysis and to ask for additional information.

The search was last run on April 8th, 2016.

Searching other resources

We handsearched the bibliographies of retrieved articles and the abstracts of conference proceedings published in Anaesthesia and Intensive Care; Anaesthesia and Analgesia; British Journal of Surgery; Critical Care Medicine; Journal of Vascular Surgery and Trauma; Injury; andInfection and Critical Care for the years 2000 to 2006.

Data collection and analysis

Selection of studies

Vivian McAlister (VM) with Brad Shrum (BS) scanned titles and abstracts identified by the initial search to exclude overlapped and irrelevant studies. Three authors (Tammy Znajda (TZ), Karen Burns (KB) and BS) identified trials that met our inclusion criteria. Brian Church (BC) resolved differences in data recorded and we resolved all differences of opinion through discussion.

Data extraction and management

At least two of the review authors abstracted data independently from the studies, using standardized forms developed for this review. We wrote to primary study authors for information regarding missing data or data that were not clearly stated. We resolved differences of opinion through discussion. We abstracted data pertaining to the included participants, interventions applied and outcomes reported for each trial. Where translation was needed we sought the help of native speakers of the language who had scientific training. The translator collected relevant information on the data collection forms provided.

We abstracted the following details from each of the included studies:

  1. Participants (inclusion and exclusion criteria; mean age; proportion of men; aetiology of disease; weight before and after surgery; serum electrolytes before, during and after surgery);

  2. Interventions (type of surgery; concentration and volume of hypertonic saline given; total volume of fluid administered and concomitant therapy);

  3. Trials (setting; methodological quality; publication status; duration of follow-up and all outcomes).

Assessment of risk of bias in included studies

We based our assessment of 'Risk of bias' on the recommendations provided in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). The assessments were based on the allocation sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting, and other potential biases (Lundh 2012; Wood 2008).

Allocation sequence generation

Low risk of bias: sequence generation was achieved using computer random-number generation or a random-number table. Drawing lots, tossing a coin, shuffling cards, and throwing dice were adequate if performed by an independent person not otherwise involved in the trial.

Uncertain risk of bias: the method of sequence generation was not specified.

High risk of bias: the sequence generation method was not random.

Allocation concealment

Low risk of bias: the participant allocations could not have been foreseen in advance of, or during, enrolment. Allocation was controlled by a central and independent randomization unit. The allocation sequence was unknown to the investigators (for example, if the allocation sequence was hidden in sequentially-numbered, opaque, and sealed envelopes).

Uncertain risk of bias: the method used to conceal the allocation was not described so that intervention allocations may have been foreseen in advance of, or during, enrolment.

High risk of bias: the allocation sequence was likely to be known to the investigators who assigned the participants.

Blinding of participants, personnel, and outcome assessors

Low risk of bias: blinding was performed adequately. Additionally, we defined lack of blinding (detection and performance bias) as not likely to affect the assessment of the outcome mortality.

Uncertain risk of bias: there was insufficient information to assess whether blinding was likely to introduce bias in the results.

High risk of bias: no blinding or incomplete blinding, and the assessment of outcomes were likely to be influenced by lack of blinding (all other outcomes than mortality and non-subjective laboratory measures).

Incomplete outcome data

Low risk of bias: missing data were unlikely to make treatment effects depart from plausible values. Sufficient methods, such as multiple imputation, were employed to handle missing data.

Uncertain risk of bias: there was insufficient information to assess whether missing data in combination with the method used to handle missing data were likely to introduce bias in the results

High risk of bias: the results were likely to be biased due to missing data.

Selective outcome reporting

Low risk of bias: the trial reported clinically relevant outcomes, which we defined as mortality, hepatic encephalopathy, and serious adverse events. If we had access to the original trial protocol, the outcomes should be those specified in that protocol. If we obtained the protocol from a trial registry such as www.clinicaltrials.gov, we only used the information if the investigators registered the trial before inclusion of the first participant.

Unclear risk of bias: not all predefined criteria were reported fully, or it was unclear whether data on these outcomes were recorded or not.

High risk of bias: one or more predefined outcomes were not reported.

Other bias

Low risk of bias: the trial appeared to be free of other bias domains, including: medicinal dosing problems or follow-up (as defined below).

Uncertain risk of bias: the trial may or may not have been free of other domains that could put it at risk of bias.

High risk of bias: there were other factors in the trial that could put it at risk of bias, such as the administration of inappropriate treatments being given to the controls (e.g. an inappropriate dose) or follow-up (e.g. the trial included different follow-up schedules for participants in the allocation groups being compared).

Evidence Quality

The control of bias in the included trials was part of the overall assessment of the quality of the body of evidence, which we classified as ‘High’, ‘Moderate’, ‘Low’, or ‘Very Low’. We based the assessment on the specific evidence grading system developed by the GRADE collaboration (GRADE 2004).

Measures of treatment effect

We performed the analyses in Review Manager 5 (RevMan 2014). We used the result value and number of participants in all intervention arms to calculate the mean difference (MD) for continuous outcomes, with 95% confidence intervals (CIs).

Unit of analysis issues

If the standard error of the mean was recorded in a study, we converted it to standard deviation following the Cochrane Handbook for Systematic Reviews of Interventions chapter 7.7.3.2. Briefly, SD = SE x Sqrt(n).

Dealing with missing data

We used the last observed response carried forward (LOCF) for participants with missing data.

Assessment of heterogeneity

We assessed heterogeneity visually through the use of funnel plots and further assessed it using the I² value. We explored sources of heterogeneity through sensitivity, subgroup, and meta-regression analyses. The analyses included the extracted participant, intervention, and trial characteristics listed above as explanatory variables.

Assessment of reporting biases

We used funnel plot asymmetry to detect reporting biases where there were more than nine studies, to avoid false detections (Sterne 2001a; Sterne 2001b). Where funnel plots appeared to have asymmetry, we deployed the test by Matthias Egger (Egger 1997) as described by the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011): linear regression of intervention effect estimate against its standard error, weighted by the inverse of the variance of the intervention effect estimate. We considered reporting biases to be evident where P < 0.05.

Data synthesis

We combined data in fixed-effect meta-analysis if the group I² was less than 30%. Where I² was 30% or greater, we used random-effects meta-analyses. We conducted intention-to-treat (ITT) analyses including all participants irrespective of compliance or follow-up. In studies that had more than two treatment arms, we incorporated only two arms of the trial into the meta-analysis: the arm using IS and the treatment arm evaluating HS solution. If there were two HS arms, we selected the one most different in concentration from IS for analysis. Where meta-analysis was not possible due to a lack of events we used the Clopper-Pearson method to estimate treatment group CIs (Clopper 1934).

Summary of findings table

We summarize the compiled data for this meta-analysis in the Summary of findings for the main comparison. Each outcome is shown with its anticipated incidence per 1000 people for each treatment group. The MD is shown with 95% CIs for continuous outcomes. The overall quality of the evidence for each outcome has been determined using the Guideline Development Tool from the GRADE working group criteria and that of Cochrane (GRADE 2004; Higgins 2011). We rated the quality of the evidence as high, moderate, low, or very low, and have shown it visually and textually. Where studies have been downgraded from high quality, we have used footnotes to indicate the reason. Notes are included for each outcome to briefly describe it, and if appropriate the method of measurement.

Subgroup analysis and investigation of heterogeneity

When appropriate after consideration of statistical and clinical heterogeneity, we performed subgroup analyses based on the following a priori criteria:

  1. Type of surgery

  2. Dose of HS: trials were stratified into three comparisons according to the dose of HS, calculated as the volume of 3% HS required to give the same amount of sodium: 7 mL/kg or less (comparison 01); 7.1 to 10 mL/kg (comparison 02); > 10 mL/kg (comparison 03). We specified these dose stratifications before the review was conducted on the basis of an anticipated range of HS doses

  3. Volume of crystalloid given to the control group: trials were stratified into three comparisons according to the total volume of fluid transfusion received by IS participants: < 2 L (comparison 01); 2 L to 5 L (comparison 02); > 5 L (comparison 03). We specified these volume stratifications in advance of the review on the basis of an anticipated range of peri-operative fluid administration

We interpreted a lack of overlap between two CIs in the subgroup analyses as representing a statistically significant difference.

Sensitivity analysis

Where the data permitted we performed a sensitivity analysis using the following a priori criteria. We removed studies that were deemed to have a moderate or higher risk of bias based on the aforementioned criteria (see Assessment of reporting biases). Where potential for bias was uncertain the review authors considered the potential impact of each domain on the results. For the purposes of sensitivity analysis, unknown sequence randomization or allocation concealment did not increase the risk of bias in a study, but unknown or high risk in any other domains did increased the risk of bias.

Results

Description of studies

Results of the search

From 284 reports identified by the search strategy, 25 reports met the criteria for further assessment (Figure 1). Of these 25 references, we excluded seven studies after detailed review because they were not randomized (Auler 1987; Shao 2005), did not compare to an IS group (Li 2014; Li 2015), or did not report our desired primary or secondary outcomes (Auler 1992; Yang Z 2014; Yousefshahi F 2013) (see Characteristics of excluded studies). We found no recently completed studies in registries of clinical trials including clinicaltrials.gov/; www.controlled-trials.com/; and www.ifpma.org/clinicaltrials.html.

Figure 1.

Study flow diagram.

Included studies

Eighteen studies with 1087 participants were included (Baraka 1994; Bruegger 2005; Cross 1989; Durasnel 1999; Ishikawa 1996; Jarvela 2000; Jarvela 2001; Kato 1996; Kimura 1994; Kølsen-Petersen 2004; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Veroli 1992; Wang 1997; Younes 1988) (see Characteristics of included studies). The included trials were performed in a wide variety of surgical situations: aortic surgery (four trials) (Bruegger 2005; Shackford 1983; Shackford 1987; Younes 1988); lower limb surgery (three trials) (Ishikawa 1996; Jarvela 2000; Veroli 1992); transurethral prostate resection (three trials) (Baraka 1994; Kato 1996; Kimura 1994); coronary artery bypass grafting (three trials) (Cross 1989; Jarvela 2001; Leverve 2008); hysterectomy (one trial) (Kølsen-Petersen 2004); hernia repair (one trial) (Wang 1997); general surgery (one trial) (Durasnel 1999); pancreaticoduodenectomy (one trial) (Lavu 2014); and neurological surgery (one trial) (Shao 2013). Anaesthetic techniques included: general anaesthesia (ten trials) (Bruegger 2005; Cross 1989; Jarvela 2001; Kato 1996; Kølsen-Petersen 2004; Lavu 2014; Shackford 1983; Shackford 1987; Shao 2013; Younes 1988) and spinal anaesthesia (seven trials) (Baraka 1994; Durasnel 1999; Ishikawa 1996; Jarvela 2000; Kimura 1994; Veroli 1992; Wang 1997).

Studies were performed in 11 countries, which include Brazil, China, Denmark, Finland, France, Germany, Indonesia, Japan, Lebanon, Niger, and USA. Four publications were written in languages other than English, including Japanese (two trials) (Ishikawa 1996; Kimura 1994); French (one trial) (Durasnel 1999); Portuguese (one trial) (Younes 1988). The majority of included studies had small sample sizes, enrolling between 20 and 72 participants. The largest study enrolled 259 participants (Lavu 2014). The interval between the first and last study was approximately 30 years (1983 to 2014). Only one of the studies was designed to determine differences in short-term mortality (Lavu 2014), with the remaining studies focusing on fluid and haemodynamic measurement during the peri-operative period. Follow-up extended into the postoperative period in 10 trials (Bruegger 2005; Cross 1989; Jarvela 2000; Jarvela 2001; Kato 1996; Kølsen-Petersen 2004; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987), with durations ranging from the stay in the recovery unit to 90 days postoperative, while the other trials confined their observations to the period of anaesthesia. Two studies reported results with standard error which we converted to standard deviation by multiplication with the square root of the number in the group (Shackford 1983; Shackford 1987).

Two authors of included studies whom we contacted for further information responded. Dr. Lavu kindly provided mean and standard deviation values that were not available in the publication (Lavu 2014), and Dr. Jarvela provided additional methodological details regarding random sequence generation and allocation concealment for two studies (Jarvela 2000; Jarvela 2001). Dr. Shao was contacted regarding methodology but did not respond (Shao 2013).

Excluded studies

Seven studies were found but ultimately excluded from analysis; two due to a lack of randomization (Auler 1987; Shao 2005), two because there was no isotonic saline control group (Li 2014; Li 2015), and three due to an absence of primary or secondary outcomes (Auler 1992; Yang Z 2014; Yousefshahi F 2013). Dr. Yousefshahi was contacted for further information but did not respond (Yousefshahi F 2013).

Risk of bias in included studies

The overall risk of bias in the included studies is undetermined due to a large number of studies (72%) not fully reporting methodology (Characteristics of included studies). The domains with the largest potential for bias are for performance and detection bias. For performance and detection bias, eight studies did not provide sufficient information to determine the potential for bias (Baraka 1994; Bruegger 2005; Durasnel 1999; Jarvela 2000; Kimura 1994; Leverve 2008; Wang 1997; Younes 1988) and five studies did not protect their studies from performance or detection bias (Ishikawa 1996; Jarvela 2001; Shackford 1983; Shackford 1987; Shao 2013). Despite there being limited or unknown protection from performance bias it is unlikely that participants were informed of the fluid given to them for resuscitation. However, care givers and outcome assessors were either not blinded or insufficient information was given to determine the risk of bias, although this is unlikely to impact the majority of our measured outcomes, including mortality (Analysis 1.1), serious adverse events (Analysis 1.2), peak and final serum sodium (Analysis 1.6, Analysis 1.7), and maximum intraoperative serum osmolarity (Analysis 1.8), pulmonary artery wedge pressure (Analysis 1.9), and cardiac index (Analysis 1.10). Performance and detection bias could impact the results of fluid measurements, leaving the outcomes of fluid balance (Analysis 1.3), total volume of crystalloid administered (Analysis 1.4), and diuresis during study period (Analysis 1.5), at a greater risk of this source of bias and overall bias (Figure 2; Figure 3).

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Figure 3.

Risk of bias summary: review authors' judgements about each 'Risk of bias' item for each included study.

Allocation

Four trials described adequate random sequence generation (Cross 1989; Jarvela 2001; Kølsen-Petersen 2004; Lavu 2014), using a table of random numbers or computer-generated random numbers. The remaining 14 studies alluded to randomization but did not describe the method used (Baraka 1994; Bruegger 2005; Durasnel 1999; Ishikawa 1996; Jarvela 2000; Kato 1996; Kimura 1994; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Veroli 1992; Wang 1997; Younes 1988).

Adequate allocation concealment was reported in six trials, four in the publication (Cross 1989; Kølsen-Petersen 2004; Lavu 2014; Shao 2013) and two through correspondence with the author (Jarvela 2000; Jarvela 2001).

From our assessment, four trials had a low risk of selection bias (Cross 1989; Jarvela 2001; Kølsen-Petersen 2004; Lavu 2014) (Characteristics of included studies).

Blinding

Five studies reported adequate concealment of treatment from participants, personnel, and outcome assessors (Cross 1989; Kato 1996; Kølsen-Petersen 2004; Lavu 2014; Veroli 1992); we have rated them as having a low risk of performance and detection bias (Characteristics of included studies).

Incomplete outcome data

We assessed 16 trials at a low risk of attrition bias (Baraka 1994; Bruegger 2005; Cross 1989; Jarvela 2000; Jarvela 2001;Kato 1996; Kimura 1994; Kølsen-Petersen 2004; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Veroli 1992; Wang 1997; Younes 1988). Each of the 16 studies provided clear information about all participants including those with missing outcome data (Characteristics of included studies).

Of the 1121 enrolled participants, 1087 completed the protocol. Four participants in the HS group failed to complete the study, one because of consent withdrawal (Kølsen-Petersen 2004); one for an anaphylactic reaction to another medication (Kølsen-Petersen 2004); one because of operative complication which met a priori exclusion criteria (Lavu 2014); and one without a reason specified (Durasnel 1999). Seven participants in the IS group failed to complete the protocol, four because of operative complications which met a priori exclusion criteria (Lavu 2014), one because of an urgent return to the operating room for control of haemorrhage (Kølsen-Petersen 2004); one because of a transfer to another hospital (Kølsen-Petersen 2004) and one without a reason specified (Durasnel 1999). Twenty-three participants failed to complete the protocol and were withdrawn from the studies without further information (Ishikawa 1996; Leverve 2008). One participant was withdrawn from Ishikawa 1996, while the other study had 22 people removed from the analysis due to major protocol violation or incomplete data collection, although they were still included in the safety profile (Leverve 2008).

Selective reporting

Seventeen of the studies reported all of the clinically relevant outcomes that were appropriate for their trial design (Baraka 1994; Cross 1989; Durasnel 1999; Ishikawa 1996; Jarvela 2000; Jarvela 2001; Kato 1996; Kimura 1994; Kølsen-Petersen 2004; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Veroli 1992; Wang 1997; Younes 1988) (Figure 2; Figure 3). However, only one of the studies explicitly reported mortality (Lavu 2014). The remaining studies imply there were no deaths through their other outcome data and we have assessed them to be at an unclear risk of reporting bias (Figure 3). Additionally, the study by Bruegger 2005 reported a disproportionately low number of female participants and we have assessed this as an unclear risk of bias because it was not explained.

Other potential sources of bias

Baseline parameters were reported in each study and appeared to be similar in both study groups in all trials. We found no evidence for other sources of bias in any of the studies (Characteristics of included studies).

Effects of interventions

See: Summary of findings for the main comparison Hypertonic salt compared to isotonic salt solution for peri-operative resuscitation

Primary outcomes

1. Mortality

One trial reported occurrences of deaths (Lavu 2014), four in the HS group and three in the IS group. From all of the studies there were 545 participants in the HS group and 542 in the IS group. Because only one study reported events an analysis to compare treatment groups could not be performed. Assessment of the HS group using the Clopper-Person estimation shows that the upper bound for occurrences of events using a 95% CI is 0.019 (19/1000). Due to the paucity of events, neither a sensitivity nor subgroup analysis was feasible. We determine the quality of the evidence is very low (Summary of findings for the main comparison).

2. Serious adverse events

There were no reports of serious adverse events such as organ failure, myocardial infarction, cerebrovascular accident or central pontine myelinolysis reported in the trials. The outcome was not explicitly measured and we have extrapolated the data. There were 1087 participants, 542 in the IS group and 545 in the HS group. Although an analysis comparing the treatment groups cannot be performed, assessment of the HS group utilizing the Clopper-Pearson estimation shows that the upper bound for occurrences of events using a 95% CI is 0.007 (7/1000). We have graded the quality of the evidence for this outcome as very low (Summary of findings for the main comparison).

Secondary outcomes
3. Fluid balance

Peri-operative fluid balance was calculated in eight trials with 737 participants (51.1% HS, 48.9% IS) (Bruegger 2005; Cross 1989; Jarvela 2001;Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013). Overall, the fluid balance was positive in both groups (Summary of findings for the main comparison), the mean volume for the IS group being 4.4 L and 1.9 L lower for the HS group (MD -1.92, 95% CI -2.61 to -1.22; I² = 91%; P < 0.00001; Analysis 1.3). We rate the quality of this evidence as low (Summary of findings for the main comparison).

We conducted a sensitivity analysis using only studies deemed to have a low risk of bias (Cross 1989; Lavu 2014). The fluid balance was again found to be statistically significantly lower for the HS group (MD -1.47, 95% CI -2.84 to -0.09; participants = 279; P = 0.04; I² = 60%; Analysis 2.1).

Subgroup analysis suggested no significant effect of the type of surgery (Analysis 3.1), dose of HS given (Analysis 3.2), or the total volume of fluid transfused (Analysis 3.3). There were too few studies to adequately investigate the high levels of heterogeneity.

4. Total volume of crystalloid administered

The volume of intravenous fluid administered to participants was reported in 13 trials with 871 participants (51.3% HS, 48.7% IS) (Bruegger 2005; Cross 1989; Durasnel 1999; Ishikawa 1996; Jarvela 2000; Jarvela 2001; Kato 1996; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Younes 1988). IS participants received a mean volume of 2.4 L (Summary of findings for the main comparison). Participants in the HS group received 1.49 L, considerably less fluid intravenously than those in the IS group (MD -0.91, 95% CI -1.24 to -0.59; I² = 99%; P < 0.00001; Analysis 1.4). We rate the quality of the evidence for this outcome as moderate (Summary of findings for the main comparison).

We conducted a sensitivity analysis to include only studies deemed to be at low risk of bias (Cross 1989; Kato 1996; Lavu 2014). We found that the amount of fluid used in the HS group was still statistically significantly less than in the IS group (MD -1.08, 95% CI -1.92 to -0.24; I² = 75%; P = 0.01; Analysis 2.2).

A subgroup analysis according to type of surgery (Analysis 3.4) and the dose of HS (Analysis 3.5) did not reveal differences between the subgroups. The high degree of heterogeneity for this outcome was not explained by subgroup analysis according to type of surgery (Analysis 3.4) or the dose of HS (Analysis 3.5). Funnel plot analysis showed this outcome to cluster symmetrically (Figure 4), except for three outliers from studies that used considerably more HS than other trials (Lavu 2014; Shackford 1983; Shackford 1987). However, exclusion of these three trials from the analysis did not eliminate heterogeneity.

Figure 4.

Funnel plot of comparison: 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, outcome: 1.4 Total volume of crystalloid administered (L).

5. Diuresis during study period

Urine output during the trial was reported in nine trials including 777 participants (51.1% HS, 48.9% IS) (Bruegger 2005; Cross 1989; Jarvela 2000; Jarvela 2001; Lavu 2014; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013). There was no difference in peri-operative urine output (L) between the two groups (MD 0.11, 95% CI -0.09 to 0.31; I² = 69%; P = 0.28; Analysis 1.5). We rate the quality of the evidence to be low for risk of bias (downgraded one level because the majority of the studies have not confirmed blinding of outcome assessors, and bias could seriously impact this result) and imprecision (downgraded one level: the volume of crystalloid solution delivered has a large range between studies).

A sensitivity analysis limited to studies with a low risk of bias (Cross 1989; Lavu 2014) did not change the findings of the outcome (MD 1.25, 95% CI -1.17 to 3.67; studies = 2; I² = 33%; Analysis 2.3).

Stratification by type of surgery (Analysis 3.6), dose of HS (Analysis 3.7), or the total volume of crystalloid use in the IS group (Analysis 3.8) did not alter the outcome or the degree of heterogeneity.

6. Peak serum sodium

The maximum serum sodium was measured in all but two trials (Durasnel 1999; Lavu 2014), and included 780 participants (50.6% HS, 49.4% IS) from 16 trials. Maximum serum sodium was higher in the HS group than the IS group, 147.4 versus 139.1 meq/L (MD 7.73, 95% CI 5.84 to 9.62; I² = 97%; P < 0.00001; Analysis 1.6). The maximum average serum sodium ranged between 138.5 and 159 in HS groups compared to between 136 and 143 meq/L in the IS groups. We rate the quality of the evidence as moderate for this outcome (Summary of findings for the main comparison).

Sensitivity analysis restricted to studies with a low risk of bias did not change the outcome or the heterogeneity of the studies (Analysis 2.4).

Subgroup analysis by type of surgery (Analysis 3.9), the dose of crystalloid administered (Analysis 3.10), or by volume of HS (Analysis 3.11) did not alter the outcome or the heterogeneity between trials. Funnel plot analysis which showed peak serum sodium of each study clusters symmetrically around a positive MD. There is substantial overlap of MD from each study, regardless of the dose of HS given (Figure 5).

Figure 5.

Funnel plot of comparison: 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, outcome: 3.10 Peak serum sodium (meq/L) by dose of HS.

7. Final serum sodium

Twelve studies with 640 participants (51.4% HS, 48.6% IS) reported final serum sodium (Bruegger 2005; Cross 1989; Jarvela 2000; Jarvela 2001; Kato 1996; Kølsen-Petersen 2004; Leverve 2008; Shackford 1983; Shackford 1987; Shao 2013; Wang 1997; Younes 1988). By the end of the study period the serum sodium mean difference between the groups was considerably reduced from those reported at peak (MD 3.45, 95% CI 2.46 to 4.44; I² = 88%, P < 0.00001; Analysis 1.7) and the range for final average serum sodium was within normal limits: 136 to 146 meq/L and 136 to 140 meq/L in the HS and IS groups respectively. We assess the quality of this evidence as moderate (Summary of findings for the main comparison).

A sensitivity analysis restricted to studies with a low risk of bias did not change the outcome or heterogeneity (Analysis 2.5).

Neither the result nor heterogeneity were altered in subgroup analysis by surgery type (Analysis 3.12), dose of HS (Analysis 3.13) or volume of crystalloid (Analysis 3.14).

8 - 10. Duration of endotracheal intubation, intensive care stay and hospital stay

None of the trials reported the duration of mechanical ventilation and the length of stay in hospital. Only one trial (Cross 1989) reported the length of stay in intensive care, with mean stays (standard deviation) of 2.3 (0.2) versus 2.4 (0.6) days in the HS and IS groups respectively (P = 0.63).

11. Other outcomes of interest

Ten trials with 369 participants (50.9% HS, 49.1% IS) (Ishikawa 1996; Jarvela 2000; Jarvela 2001; Kato 1996; Kimura 1994; Kølsen-Petersen 2004; Shackford 1983; Shackford 1987; Shao 2013; Younes 1988) reported maximum serum osmolarity (Analysis 1.8). We found that there was a statistically significant increase in serum osmolarity with HS, increased 5.3% from the median level of 289 mOsm/kg H20 in the IS group (MD 15.29 mOsm/kg H2O higher with HS, 95% CI 12.27 to 18.31; I² = 86%, P < 0.00001). We assess the quality of the evidence to be moderate. We downgraded the study quality because of a high degree of heterogeneity that probably derives from the wide range of crystalloid fluid given across the studies. Future high-quality studies are likely to change this result.

Intraoperative pulmonary artery wedge pressure (Analysis 1.9) was reported in three studies with 150 participants (50.7% HS, 49.3% IS) (Jarvela 2001; Shackford 1983; Shackford 1987). There was no difference between the treatment groups (MD 0.16, 95% CI -1.69 to 2.02; I² = 0%; P = 0.86).

Maximum intraoperative cardiac index was reported in six studies with 418 participants (51.7% HS, 48.3% IS) (Cross 1989; Jarvela 2000; Jarvela 2001; Leverve 2008; Shackford 1983; Shackford 1987). We found that the maximum intraoperative cardiac index was elevated 11.7% in the HS group over the median level of 2.9 L/min/m² in the IS group (MD 0.34, 95% CI 0.19 to 0.49; I² = 40%; P = 0.0001; Analysis 1.10). We rate the quality of these data to be high (Summary of findings for the main comparison).

Although only one of the trials (Lavu 2014) specifically reported adverse events, they have not met our criteria to be considered serious adverse events. Adverse events were reported over a 90-day follow-up period and the study found no difference between the HS and IS groups.

Discussion

Summary of main results

It was not possible to determine differences with respect to mortality or major morbidity between the treatment arms of this meta-analysis. A preliminary survey carried out before designing the meta-analysis suggested that trials of peri-operative HS were usually designed to measure fluid volumes, haemodynamics and biochemistry rather than measure important clinical outcomes. Despite this, we chose mortality as the primary outcome for this review and we collected serious adverse event data because of their clinical importance.

Peri-operative diuresis was similar in the HS and IS participants, suggesting that adequate intravascular volumes were maintained throughout surgery despite the fact that HS participants received significantly less intravenous fluid than IS participants (Summary of findings for the main comparison). All of the participant groups completed surgery with a positive fluid balance (Summary of findings for the main comparison). In some trials, the positive fluid balance was almost 10 L by the end of surgery. Pulmonary oedema was not recorded in the trials but it is reasonable to be concerned that excess fluid of this magnitude would result in pulmonary oedema in a population at risk of this complication. Use of HS significantly reduced the positive fluid balance experienced by all participants undergoing surgery. HS increased serum sodium and osmolarity (Summary of findings for the main comparison). The doses of HS varied considerably between trials, but even in those who received very high doses of HS no adverse events related to hypernatraemia were encountered. Serum sodium returned to normal limits by the end of the study.

Overall completeness and applicability of evidence

Meta-analysis of the outcomes measured by the trials provides a reasonably complete picture of the immediate impact of HS on peri-operative fluid management. HS significantly reduces the positive fluid balance experienced by people undergoing surgery while maintaining a stable haemodynamic state. This observation was independent of the type of surgery or whether peri-operative fluid protocol was restricted or unrestricted by volume. HS conserved fluid at lower doses as much as at higher doses. However the trials were not designed to look at the impact of the interventions on mortality or longer-term morbidity.

To date, we have only found one trial where mortality and adverse events were explicitly measured over a period that extended beyond the original hospital stay (Lavu 2014). Mortality at 90 days did not differ between treatment groups of participants undergoing pancreaticoduodenectomy, but there is no evidence to suggest that this result would remain true at different centres or for different procedures. Until there are more, high-power studies examining mortality in different surgical procedures at multiple centres, we cannot say with certainty that there is no effect of HS on mortality. This same study also measured postoperative complications (non-serious adverse events). Although the result was not statistically significant, there were over 10% more postoperative complications in the IS group. Future trials will be necessary to test this finding.

This review showed that people receiving HS had a transient increase in serum sodium (Summary of findings for the main comparison). Hypernatraemia has the potential to harm but this was not seen in the included studies. In hyponatraemic people, the risk of central pontine myelinolysis is thought to be related to underlying conditions more than the rate of electrolyte repletion, but increases in serum sodium of more than 10 meq/L per day should be avoided if possible (Kumar 2006). It is not known if people with normal serum sodium are at a similar risk of hyperosmotically induced demyelination. No episodes of central pontine myelinolysis were reported in these studies where the participants had normal serum sodium levels at baseline, and we did not find any case reports in the literature of central pontine myelinolysis in people who received HS.

Is there a potential therapeutic window for HS in people undergoing surgery, where peri-operative weight gain can be minimized without a risk of significant hypernatraemia? Hypernatraemia is transient after administration of HS. However, it would seem prudent to avoid large increases in serum sodium. This is possible, with these studies suggesting that up to 10 ml/kg of 3% HS will reduce the positive fluid balance peri-operatively by up to 1.5 L in the average adult without increasing serum sodium inappropriately. There is insufficient evidence to determine if such a reduction in peri-operative fluid excess would improve clinically relevant outcomes but it provides the basis for an RCT.

The evidence is strong for a reduction in the volume of peri-operative fluid required to maintain homeostasis with HS. There is no direct evidence that this results in better survival or quality of life. The principal barrier to meta-analysis of some outcomes is a high degree of heterogeneity between the trials. Heterogeneity appears to be due to differences in the magnitude of the effect observed rather than differences in the effect itself. Subgroup analysis identified sources of heterogeneity in some instances. For example, there was considerable heterogeneity in peri-operative diuresis even though there was no significant difference in diuresis between the test group, HS, and the control.

Overall there is a strong need for well-controlled, high-quality studies with adequate design to measure both short- and long-term variables. The results of this systematic review and future studies could prove to be very important to patient care, particularly when low volumes of resuscitating fluid are needed. At this time the results show promise for HS as a safe choice for resuscitation during surgery where reduced volumes would be beneficial, but more evidence is needed.

Quality of the evidence

The quality of evidence across these trials ranged from high to very low. The majority of trials included in this study cover relatively few participants. The trials were conducted in several eras when other peri-operative practices may have changed. There was also a large variation in the dose of HS given between studies which may have resulted in the high heterogeneity between them. Furthermore, many of the studies did not specify the methods of allocation concealment or randomization, which again probably reflects the era in which many of the studies were reported.

For determining mortality, the trials lacked sufficient size, duration and reporting to adequately assess important differences. Furthermore, only one study (Lavu 2014) explicitly reported the outcome, and we have extrapolated the data on the basis that other outcomes were reported by each study for all included participants. We have assessed the quality of evidence for mortality to be very low, and future studies are likely to change the result reported here (Summary of findings for the main comparison).

We rate the quality of the evidence for fluid balance and diuresis to be low (Summary of findings for the main comparison). There is a systemic lack of blinding of personnel across these studies, leaving these outcomes prone to bias. High-quality study results are likely to change this outcome.

The reporting of peak and final serum sodium is of moderate quality (Summary of findings for the main comparison). The level of blood sodium during surgery is a common hospital measurement that is unlikely to be biased. The difference in the number of samples collected by the different studies impacts the quality of this outcome. Future studies are likely to change this result.

We have rated the quality of the evidence for the maximum intraoperative cardiac index as high (Summary of findings for the main comparison). The measurement during an operation is a common hospital procedure that is unlikely to be biased. The studies that report this outcome are well controlled, and the values reported are consistent across the studies. Future studies are unlikely to change this result.

Potential biases in the review process

Having searched the largest medical research data bases, without limit by language of publication, it is highly likely that we have found all published data that met our inclusion criteria.

The review authors tried to reduce the impact of personal bias in the presentation and analysis of the results. When assessing the degree that individual bias components would impact study results, we have undoubtedly relied on our own experiences. We have assumed, in cases where the information was not available, that the reports were conducted by compassionate physicians and dedicated researchers who have performed their work honestly and to the best of their abilities. Because of this, we have left our analysis open to being impacted by fraudulent reports.

Agreements and disagreements with other studies or reviews

This is the first systematic review of HS compared to IS for peri-operative fluid management. This update confirms the findings of the first version (McAlister 2006). The findings are consistent with reviews of HS given for other indications such as fluid management in people with burns (Bunn 2004).

Authors' conclusions

Implications for practice

There was insufficient evidence from the included studies to suggest that the use of HS confers any clinical benefit or harm in terms of mortality or major morbidity compared to the use of IS. There is no reason to prefer HS for the routine management of people having surgery. The reduction in positive fluid balance when using HS may suggest HS would be an appropriate choice when fluid restriction is required in selected individuals or clinical situations.

Implications for research

HS administration to people undergoing surgery should be compared to standard practice, using RCTs of high methodological rigour in order to determine any impact on participant survival and other clinically relevant outcomes. Sample size estimation is problematic, given the very low reported incidence of mortality or significant morbidity in the control groups in these trials. The duration of any future trial should be sufficient to cover the period of peri-operative mortality or major morbidity which is usually considered to be 60 days or at least the postoperative hospital stay.

Acknowledgements

We would like to thank Associate Professor Mike Bennett (content editor), Dr Harald Herkner (statistical editor), Dr Nathan Pace (statistical editor), Dr Thomas Schricker, Dr Birgitte Brandstrup (peer reviewers) and Rosemary Doolan (consumer) for their help and editorial advice during the preparation of the protocol and review (McAlister 2006; McAlister 2010). We also acknowledge the help of the copy editor, Kate Cahill, in preparation of this manuscript.

Mark Edward, Kathie Godfrey and Nete Villebro for their help and editorial advice during the preparation of the protocol for the review (McAlister 2006); Mr Karen Hovhannisyan, former Trials Search Co-ordinator of the Cochrane Anaesthesia; Critical and Emergency Care Group, for advice regarding electronic searches; Dr Hideaki Tanaka, Ms Christiane Baldwin and Dr Yoshihisa Morita for translations; and Mrs Jane Cracknell, Managing Editor of the Cochrane Anaesthesia, Critical and Emergency Care Group, for patient guidance throughout the whole process. Dr Tammy Znajda was a co-author on the first version of this review. - in the 'Contributions of authors', Dr Znajda's contributions relate to the first review only (McAlister 2010).

Data and analyses

Download statistical data

Comparison 1. Hypertonic salt versus isotonic salt solution for peri-operative resuscitation
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Mortality during the study period181087Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
2 Serious adverse events during the study period181087Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]
3 Fluid balance (L) measured at the end of the recovery period8737Mean Difference (IV, Random, 95% CI)-1.92 [-2.61, -1.22]
4 Total volume of crystalloid administered (L)13871Mean Difference (IV, Random, 95% CI)-0.91 [-1.24, -0.59]
5 Diuresis during study period (L)9777Mean Difference (IV, Random, 95% CI)0.11 [-0.09, 0.31]
6 Peak serum sodium (meq/L)16780Mean Difference (IV, Random, 95% CI)7.73 [5.84, 9.62]
7 Final serum sodium (meq/L)12640Mean Difference (IV, Random, 95% CI)3.45 [2.46, 4.44]
8 Maximum intraoperative serum osmolarity (mOsm/kg H2O)10369Mean Difference (IV, Random, 95% CI)15.29 [12.27, 18.31]
9 Maximum intraoperative pulmonary artery wedge pressure (mm Hg)3150Mean Difference (IV, Fixed, 95% CI)0.16 [-1.69, 2.02]
10 Maximum intraoperative cardiac index (L/min/M2)6418Mean Difference (IV, Random, 95% CI)0.34 [0.19, 0.49]
Analysis 1.1.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 1 Mortality during the study period.

Analysis 1.2.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 2 Serious adverse events during the study period.

Analysis 1.3.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 3 Fluid balance (L) measured at the end of the recovery period.

Analysis 1.4.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 4 Total volume of crystalloid administered (L).

Analysis 1.5.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 5 Diuresis during study period (L).

Analysis 1.6.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 6 Peak serum sodium (meq/L).

Analysis 1.7.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 7 Final serum sodium (meq/L).

Analysis 1.8.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 8 Maximum intraoperative serum osmolarity (mOsm/kg H2O).

Analysis 1.9.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 9 Maximum intraoperative pulmonary artery wedge pressure (mm Hg).

Analysis 1.10.

Comparison 1 Hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 10 Maximum intraoperative cardiac index (L/min/M2).

Comparison 2. Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Fluid balance (L) measured during the study period: studies at low risk of bias2279Mean Difference (IV, Random, 95% CI)-1.47 [-2.84, -0.09]
2 Total volume of crystalloid administered (L): studies at low risk of bias3319Mean Difference (IV, Random, 95% CI)-1.08 [-1.92, -0.24]
3 Diuresis during study period (L): studies at low risk of bias2279Mean Difference (IV, Random, 95% CI)1.25 [-1.17, 3.67]
4 Peak serum sodium (meq/L): studies at low risk of bias4129Mean Difference (IV, Random, 95% CI)6.03 [3.96, 8.09]
5 Final serum sodium (meq/L): studies at low risk of bias399Mean Difference (IV, Random, 95% CI)2.48 [0.33, 4.62]
6 Maximum intraoperative serum osmolarity (mOsm/kg H2O): studies at low risk of bias279Mean Difference (IV, Random, 95% CI)15.81 [12.86, 18.77]
Analysis 2.1.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 1 Fluid balance (L) measured during the study period: studies at low risk of bias.

Analysis 2.2.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 2 Total volume of crystalloid administered (L): studies at low risk of bias.

Analysis 2.3.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 3 Diuresis during study period (L): studies at low risk of bias.

Analysis 2.4.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 4 Peak serum sodium (meq/L): studies at low risk of bias.

Analysis 2.5.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 5 Final serum sodium (meq/L): studies at low risk of bias.

Analysis 2.6.

Comparison 2 Sensitivity analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 6 Maximum intraoperative serum osmolarity (mOsm/kg H2O): studies at low risk of bias.

Comparison 3. Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Fluid balance (L) by type of surgery8737Mean Difference (IV, Random, 95% CI)-1.92 [-2.61, -1.22]
1.1 Aortic surgery3138Mean Difference (IV, Random, 95% CI)-3.84 [-6.45, -1.23]
1.2 Neurosurgery140Mean Difference (IV, Random, 95% CI)-1.20 [-1.59, -0.81]
1.3 Hepatobiliary surgery1259Mean Difference (IV, Random, 95% CI)-0.53 [-2.20, 1.14]
1.4 Coronary artery bypass surgery3300Mean Difference (IV, Random, 95% CI)-1.24 [-1.92, -0.57]
2 Fluid balance (L) by dose of HS8737Mean Difference (IV, Random, 95% CI)-1.91 [-2.61, -1.22]
2.1 < 7.1 mL 3% HS/kg140Mean Difference (IV, Random, 95% CI)-1.20 [-1.59, -0.81]
2.2 7.1 - 10 mL 3% HS/kg3308Mean Difference (IV, Random, 95% CI)-0.92 [-1.22, -0.62]
2.3 > 10 mL 3% HS/kg4389Mean Difference (IV, Random, 95% CI)-3.08 [-5.23, -0.94]
3 Fluid balance (L) by volume given to control group8737Mean Difference (IV, Random, 95% CI)-1.91 [-2.61, -1.22]
3.1 < 2000 mL00Mean Difference (IV, Random, 95% CI)0.0 [0.0, 0.0]
3.2 2000 - 5000 mL4328Mean Difference (IV, Random, 95% CI)-1.31 [-1.92, -0.70]
3.3 > 5000 mL4409Mean Difference (IV, Random, 95% CI)-2.87 [-5.29, -0.44]
4 Total volume of crystalloid administered (L) by type of surgery13871Mean Difference (IV, Random, 95% CI)-0.91 [-1.24, -0.59]
4.1 Cardiovascular surgery7429Mean Difference (IV, Random, 95% CI)-1.14 [-1.71, -0.57]
4.2 Non-cardiovascular surgery6442Mean Difference (IV, Random, 95% CI)-0.78 [-1.05, -0.50]
5 Total volume of crystalloid administered (L) by dose of HS13871Mean Difference (IV, Random, 95% CI)-0.91 [-1.24, -0.59]
5.1 < 7.1 mL 3% HS/kg4143Mean Difference (IV, Random, 95% CI)-0.77 [-1.19, -0.35]
5.2 7.1 - 10 mL 3% HS/kg5339Mean Difference (IV, Random, 95% CI)-0.76 [-1.25, -0.27]
5.3 > 10 mL 3% HS/kg4389Mean Difference (IV, Random, 95% CI)-2.50 [-4.99, -0.02]
6 Diuresis during study period (L) by type of surgery9777Mean Difference (IV, Random, 95% CI)0.11 [-0.10, 0.31]
6.1 Cardiovascular surgery6438Mean Difference (IV, Random, 95% CI)0.15 [-0.22, 0.52]
6.2 Non-cardiovascular surgery3339Mean Difference (IV, Random, 95% CI)0.00 [-0.30, 0.30]
7 Diuresis during study period (L) by dose of HS9777Mean Difference (IV, Random, 95% CI)0.10 [-0.10, 0.30]
7.1 < 7.1 mL 3% HS/kg140Mean Difference (IV, Random, 95% CI)-0.16 [-0.54, 0.22]
7.2 7.1 - 10 mL 3% HS/kg4348Mean Difference (IV, Random, 95% CI)0.00 [-0.12, 0.13]
7.3 > 10 mL 3% HS/kg4389Mean Difference (IV, Random, 95% CI)0.31 [-0.50, 1.11]
8 Diuresis during study period (L) by volume given to control group9777Mean Difference (IV, Random, 95% CI)0.09 [-0.11, 0.30]
8.1 < 2000 mL268Mean Difference (IV, Random, 95% CI)0.00 [-0.16, 0.17]
8.2 2000 - 5000 mL3300Mean Difference (IV, Random, 95% CI)0.33 [-0.19, 0.85]
8.3 > 5000 mL4409Mean Difference (IV, Random, 95% CI)-0.16 [-0.48, 0.17]
9 Peak serum sodium (meq/L) by type of surgery16780Mean Difference (IV, Random, 95% CI)7.73 [5.84, 9.62]
9.1 Cardiovascular surgery7469Mean Difference (IV, Random, 95% CI)10.61 [6.91, 14.31]
9.2 Transurethral resection of the prostate387Mean Difference (IV, Random, 95% CI)4.01 [1.86, 6.16]
9.3 Other surgery6224Mean Difference (IV, Random, 95% CI)6.52 [3.64, 9.40]
10 Peak serum sodium (meq/L) by dose of HS16780Mean Difference (IV, Random, 95% CI)7.73 [5.84, 9.62]
10.1 < 7.1 mL 3% HS/kg6218Mean Difference (IV, Random, 95% CI)5.31 [2.00, 8.63]
10.2 7.1 - 10 mL 3% HS/kg6418Mean Difference (IV, Random, 95% CI)8.93 [5.16, 12.70]
10.3 > 10 mL 3% HS/kg4144Mean Difference (IV, Random, 95% CI)9.75 [5.50, 13.99]
11 Peak serum sodium (meq/L) by volume given to control group11619Mean Difference (IV, Random, 95% CI)9.10 [6.66, 11.53]
11.1 < 2000 mL/kg4141Mean Difference (IV, Random, 95% CI)4.94 [3.53, 6.34]
11.2 2000 - 5000 mL4328Mean Difference (IV, Random, 95% CI)9.05 [4.54, 13.56]
11.3 > 5000 mL3150Mean Difference (IV, Random, 95% CI)13.93 [11.44, 16.42]
12 Final serum sodium (meq/L) by type of surgery12640Mean Difference (IV, Random, 95% CI)3.45 [2.46, 4.44]
12.1 Cardiovascular surgery6390Mean Difference (IV, Random, 95% CI)3.91 [2.55, 5.28]
12.2 Transurethral resection of prostate140Mean Difference (IV, Random, 95% CI)2.0 [0.45, 3.55]
12.3 Other surgery5210Mean Difference (IV, Random, 95% CI)3.05 [0.77, 5.32]
13 Final serum sodium (meq/L) by dose of HS12640Mean Difference (IV, Random, 95% CI)3.45 [2.46, 4.44]
13.1 < 7.1 mL 3% HS/kg3140Mean Difference (IV, Random, 95% CI)3.69 [1.70, 5.68]
13.2 7.1 - 10 mL 3% HS/kg6370Mean Difference (IV, Random, 95% CI)2.63 [1.17, 4.10]
13.3 > 10 mL 3% HS/kg3130Mean Difference (IV, Random, 95% CI)5.56 [3.16, 7.96]
14 Final serum sodium (meq/L) by volume given to control group9333Mean Difference (IV, Random, 95% CI)3.73 [2.29, 5.17]
14.1 < 2000 mL3111Mean Difference (IV, Random, 95% CI)2.32 [-0.74, 5.39]
14.2 2000 - 5000 mL372Mean Difference (IV, Random, 95% CI)3.14 [1.02, 5.27]
14.3 > 5000 mL3150Mean Difference (IV, Random, 95% CI)5.70 [3.98, 7.43]
Analysis 3.1.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 1 Fluid balance (L) by type of surgery.

Analysis 3.2.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 2 Fluid balance (L) by dose of HS.

Analysis 3.3.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 3 Fluid balance (L) by volume given to control group.

Analysis 3.4.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 4 Total volume of crystalloid administered (L) by type of surgery.

Analysis 3.5.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 5 Total volume of crystalloid administered (L) by dose of HS.

Analysis 3.6.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 6 Diuresis during study period (L) by type of surgery.

Analysis 3.7.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 7 Diuresis during study period (L) by dose of HS.

Analysis 3.8.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 8 Diuresis during study period (L) by volume given to control group.

Analysis 3.9.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 9 Peak serum sodium (meq/L) by type of surgery.

Analysis 3.10.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 10 Peak serum sodium (meq/L) by dose of HS.

Analysis 3.11.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 11 Peak serum sodium (meq/L) by volume given to control group.

Analysis 3.12.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 12 Final serum sodium (meq/L) by type of surgery.

Analysis 3.13.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 13 Final serum sodium (meq/L) by dose of HS.

Analysis 3.14.

Comparison 3 Subgroup analysis - hypertonic salt versus isotonic salt solution for peri-operative resuscitation, Outcome 14 Final serum sodium (meq/L) by volume given to control group.

Appendices

Appendix 1. MEDLINE (Ovid SP) 1946 to April 2007.

#1 explode saline solution, hypertonic/ all subheadings
#2 explode hypertonic solutions/ all subheadings
#3 (hypertonic NaCl) or (hypertonic saline) or (hypertonic solution*)
#4 Ringer's solution/ all subheadings
#5 #1 or #2 or #3 or #4
#6 #5 not (explode glucose solution, hypertonic / all subheadings)
#7 #6 not colloid*
#8 explode surgical procedures, operative/ all subheadings
#9 explode specialties, surgical/ all subheadings
#10 explode surgery/ all subheadings
#11 (surg* near procedur*) or surger* or operat*
#12 #8 or #9 or #10 or #11
#13 #7 and #12
#14 RANDOMIZED-CONTROLLED-TRIAL in PT
#15 CONTROLLED-CLINICAL-TRIAL in PT
#16 explode RANDOMIZED-CONTROLLED-TRIALS/ all subheadings
#17 explode RANDOM-ALLOCATION/ all subheadings
#18 explode DOUBLE-BLIND-METHOD/ all subheadings
#19 explode SINGLE-BLIND-METHOD/ all subheadings
#20 #14 or #15 or #16 or #17 or #18 or #19
#21 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#22 #20 not #21
#23 CLINICAL-TRIAL in PT
#24 explode CLINICAL-TRIALS / all subheadings
#25 (clin* near trial*) in TI
#26 (clin* near trial*) in AB
#27 (singl* or doubl* or trebl* or tripl*) near (blind* or mask*)
#28 (#27 in TI) or (#27 in AB)
#29 explode PLACEBOS/ all subheadings
#30 placebo* in TI
#31 placebo* in AB
#32 random* in TI
#33 random* in AB
#34 explode RESEARCH-DESIGN/ all subheadings
#35 #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33
or #34
#36 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#37 #35 not #36
#38 #37 not #22
#39 TG=COMPARATIVE-STUDY
#40 explode EVALUATION-STUDIES/ all subheadings
#41 explode FOLLOW-UP-STUDIES/ all subheadings
#42 explode PROSPECTIVE-STUDIES/ all subheadings
#43 control* or prospectiv* or volunteer*
#44 (#43 in TI) or (#43 in AB)
#45 #39 or #40 or #41 or #42 or #43 or #44
#46 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#47 #45 not #46
#48 #47 not (#22 or #38)
#49 #22 or #38 or #48
#50 #13 and #49

Appendix 2. EMBASE (Ovid SP) 1974 to April 2007.

#1 saline solution

#2 explode "hypertonic-solution" / all SUBHEADINGS in DEM,DER,DRM,DRR

#3 (hypertonic NaCl) or (hypertonic saline) or (hypertonic solution*)

#4 "Ringer-solution" / all SUBHEADINGS in DEM,DER,DRM,DRR

#5 sodium chloride in TI, AB

#6 #1 or #2 or #3 or #4 or #5

#7 #6 not (glucose or fructose)

#8 explode surgery/ all subheadings

#9 (surg* near procedur*) or surger* or operat*

#10 "surgical-technique" / all SUBHEADINGS in DEM,DER,DRM,DRR

#11 #8 or #9 or #10

#12 #7 and #11

#13 explode "randomized-controlled-trial" / all SUBHEADINGS in DEM,DER,DRM,DRR

#14 (randomi?ed controlled trial*) in TI, AB

#15 random*

#16 explode "randomization-" / all SUBHEADINGS in DEM,DER,DRM,DRR

#17 randomi?ation

#18 explode "clinical-trial" / all SUBHEADINGS in DEM,DER,DRM,DRR

#19 clinical near trial*

#20 explode multicenter-study / all subheadings

#21 multi?cent*

#22 explode phase-4-clinical-trial / all subheadings or explode double-blind-procedure / all subheadings or explode single-blind-procedure / all subheadings

#23 (RANDOM* or CROSS?OVER* or FACTORIAL* or PLACEBO* or VOLUNTEER*) in TI, AB, TW

#24 ((SINGL* or DOUBL* or TREBL* or TRIPL*) near (BLIND* or MASK*)) in TI,AB

#25 #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24

#26 (human) in DER

#27 (animal or nonhuman) in DER

#28 #26 and #27

#29 #27 not #28

#30 #25 not #29

#31 #12 and #30

Appendix 3. CINAHL (1982 to April 2007)

#1 explode "Saline-Solution-Hypertonic" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#2 explode "Hypertonic-Solutions" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#3 (hypertonic NaCl) or (hypertonic saline) or (hypertonic solution*)

#4 explode "Lactated-Ringer's-Solution" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#5 explode "Sodium-Chloride" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#6 #1 or #2 or #3 or #4 or #5

#7 #6 not (glucose or fructose)

#8 explode "Surgery-Operative" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#9 (surg* near procedur*) or (surg* and procedur*)or surger* or operat*

#10 #8 or #9

#11 #7 and #10

#12 Randomized Clinical Trial*

#13 Controlled Clinical Trial*

#14 explode "Random-Assignment" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#15 "Double-Blind-Studies" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#16 "Single-Blind-Studies" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#17 explode "Clinical-Trials" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#18 (clin* near trial*) in TI

#19 (clin* near trial*) in AB

#20 (singl* or doubl* or trebl* or tripl*) near (blind* or mask*)

#21 (#20 in TI) or (#20 in AB)

#22 "Placebos-" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#23 placebo* in TI

#24 placebo* in AB

#25 random* in TI

#26 random* in AB

#27 "Study-Design" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#28 "Comparative-Studies" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#29 explode "Evaluation-Research" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#30 "Prospective-Studies" / all TOPICAL SUBHEADINGS / all AGE SUBHEADINGS in DE

#31 control* or prospectiv* or volunteer*

#32 #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31

#33 sheep or dog* or cat* or guinea?pig* or mouse or experimental animal*

#34 explode animals/ all topical subheadings / all age subheadings

#35 #33 or #34

#36 human*

#37 #35 not (#34 and #35)

#38 #32 not #37

#39 #11 and #38

Appendix 4. LILACS (1982 to April 8, 2016)

"HYPERTONIC" or "HYPERTONIC SALINE SOLUTION/" or "HYPERTONIC SOLUTION, SALINE/" or "HYPERTONIC SOLUTIONS/" or "RINGER" or "SODIUM CHLORIDE" or "SODIUM CHLORIDE SOLUTION, HYPERTONIC/" [Words] and "SURGERY" or "SURGICAL" or "OPERATION" or "surg$" or "operat$" [Words]

Appendix 5. CENTRAL, (The Cochrane Library, April 2007)

#1 MeSH descriptor Sodium Chloride explode all trees
#2 MeSH descriptor Saline Solution, Hypertonic explode all trees
#3 ( (hypertonic in All Text and NaCl in All Text) or (hypertonic in All Text and saline in All Text) or (hypertonic in All Text and solution* in All Text) )
#4 (Ringer's in All Text and solution in All Text)
#5 (#1 or #2 or #3 or #4)
#6 MeSH descriptor Glucose Solution, Hypertonic explode all trees
#7 (#5 and not #6)
#8 (#7 and not colloid* in All Text)
#9 MeSH descriptor surgical procedures, operative explode all trees
#10 MeSH descriptor Specialties, Surgical explode all trees
#11 MeSH descriptor Specialties, Dental explode all trees
#12 MeSH descriptor Surgery explode all trees
#13 (surg* in All Text near/6 procedur* in All Text)
#14 (surger* in All Text or operat* in All Text)
#15 (#9 or #10 or #11 or #12 or #13 or #14)
#16 (#8 and #15)
5 not #36
#38 #37 not #22
#39 TG=COMPARATIVE-STUDY
#40 explode EVALUATION-STUDIES/ all subheadings
#41 explode FOLLOW-UP-STUDIES/ all subheadings
#42 explode PROSPECTIVE-STUDIES/ all subheadings
#43 control* or prospectiv* or volunteer*
#44 (#43 in TI) or (#43 in AB)
#45 #39 or #40 or #41 or #42 or #43 or #44
#46 (TG=ANIMALS) not ((TG=HUMAN) and (TG=ANIMALS))
#47 #45 not #46
#48 #47 not (#22 or #38)
#49 #22 or #38 or #48
#50 #13 and #49

Appendix 6. Search update: April 2007 to April 8, 2016

Search strategy for EMBASE (Ovid SP)

#1.     exp sodium chloride/ or Ringer solution/
#2.     exp hypertonic solution/
#3.     (hypertonic adj3 (NaCl or saline or solution*)).mp.
#4.     #1 or #2 or #3
#5.     (glucose or fructose).mp.
#6.     #4 not #5
#7.     surgery/ or ((surg* adj3 procedur*) or surger* or operat*).ti,ab.
#8.     (RANDOM* or CROSS?OVER* or FACTORIAL* or PLACEBO* or VOLUNTEER* or ((SINGL* or DOUBL* or TREBL* or TRIPL*) adj3 (BLIND* or MASK*))).mp. not (animal not (human and animal)).sh.
#9.     #6 and #7 and #8

Search strategy for MEDLINE (Ovid SP)

#1.     saline solution, hypertonic/ or hypertonic solutions/
#2.     (hypertonic adj3 (NaCl or saline or solution*)).mp. or ringer.mp.
#3.     #1 or #2
#4.     exp glucose solution, hypertonic/ or colloid*.mp.
#5.     #3 not #4
#6.     exp surgical procedures, operative/ or exp specialties, surgical/ or exp surgery/
#7.     ((surg* adj3 procedur*) or surger* or operat*).mp.
#8.     #6 or #7
#9.     #8 and #5
#10.     ((randomized controlled trial or controlled clinical trial).pt. or randomized.ab. or placebo.ab. or drug therapy.fs. or randomly.ab. or trial.ab. or groups.ab.) not (animals not (humans and animals)).sh.
#11.     #9 and #10


Search strategy for CINAHL (EBASCOhost)

S1. (MM "Saline Solution, Hypertonic") or (MM "Hypertonic Solutions") 
S2. (MH "Lactated Ringer's Solution") 
S3. TX (hypertonic and (NaCl or saline or solution*)) or Ringer 
S4. (MH "Sodium Chloride") 
S5. S1 or S2 or S3 or S4 
S6. TX glucose or fructose 
S7. S5 not S6 
S8. (MH "Surgery, Operative") 
S9. TX surger* or operat* 
S10. S8 or S9 
S11. S7 and S10  


Search strategy for CENTRAL, The Cochrane Library

#1    MeSH descriptor Saline Solution, Hypertonic explode all trees
#2    MeSH descriptor Hypertonic Solutions explode all trees
#3    (hypertonic NaCl) or (hypertonic saline) or (hypertonic solution*)
#4    Ringer* near solution*
#5    Sodium Chloride
#6    (#1 OR #2 OR #3 OR #4 OR #5)
#7    MeSH descriptor Glucose Solution, Hypertonic, this term only
#8    (#6 AND NOT #7)
#9    MeSH descriptor Surgical Procedures, Operative explode all trees
#10   MeSH descriptor Specialties, Surgical explode all trees
#11   MeSH descriptor Surgery explode all trees
#12   (surg* near procedur*) or surger* or operat*
#13   (#9 OR #10 OR #11 OR #12)
#14   (#8 AND #13)

What's new

DateEventDescription
8 April 2016New search has been performedIn this update, we searched CENTRAL, Pubmed, EMBASE, LILACS, and CINAHL, and reviewed the results up to April 08, 2016. We identified and screened 42 additional studies. We excluded 39 of those studies, added no studies to the 'Awaiting classification' section, or to 'Ongoing studies'. We include three new studies (Lavu 2014; Leverve 2008; Shao 2013).
8 April 2016New citation required but conclusions have not changedA new author has been added to the review team (Brad Shrum). We added three new studies which did not change the conclusions of the review. We updated the methods for the review.

Contributions of authors

Conceiving the review: T Znajda (TZ), K Burns (KB), V McAlister (VM) B Church (BC)
Co-ordinating the review: VM
Undertaking manual searches: TZ, K.B, VM, Eric McArthur (EM), BS
Screening search results: TZ, KB, VM, BC, EM, BS
Organizing retrieval of papers: TZ, VM, BS
Screening retrieved papers against inclusion criteria: TZ, KB, VM, EM, BS
Appraising quality of papers: TZ, KB, VM, EM, BS
Abstracting data from papers: TZ, KB, VM, BC, EM, BS
Writing to authors of papers for additional information: VM, BS
Obtaining and screening data on unpublished studies: TZ, KB, VM, BS
Data management for the review: TZ, KB, VM, EM
Entering data into Review Manager (RevMan 2014): VM, KB, EM, BS
RevMan statistical data: VM, KB, EM
Other statistical analysis not using RevMan: KB
Double entry of data: (data entered by person one: VM ; data entered by person two: KB ; data entered by person two alternates: EM, BS)
Interpretation of data: TZ, KB, VM, EM
Statistical analysis: TZ, KB, VM, EM
Writing the review: VM
Securing funding for the review: Not applicable
Performing previous work that was the foundation of the present study: TZ, KB, VM, BC
Guarantor for the review (one author) VM
Persons responsible for reading and checking review before submission: TZ, KB, VM, BC, EM, BS

Declarations of interest

Shrum, Bradly: none identified
McArthur, Eric: none identified
Burns, Karen: none identified
Chruch, Brian: none identified
Znadja, Tammy: none identified
McAlister, Vivian: none identified

Sources of support

Internal sources

  • Lawson Health Research Institute, Canada.

     LHRF F9738 (V McAlister Research Fund)

  • University of Western Ontario, Canada.

    Division of General Surgery Research Fund

External sources

  • No external funds sought or received, Other.

Differences between protocol and review

Bradly Shrum was added as an author since the initial publication of our protocol (McAlister 2006).

Studies did not provide data regarding duration of hospitalization, duration of endotracheal intubation, length of stay in ICU. Studies did not explicitly provide data on adverse outcomes such as: any organ failure, any requirement for dialysis (renal failure) or prolonged ventilation (pulmonary failure); use of medical therapy for either pulmonary oedema or circulatory support (cardiac failure) or for confusion (cerebral failure).

In addition to the prespecified outcomes, we also collected data regarding serum osmolarity and peri-operative haemodynamic parameters including pulmonary wedge pressure and cardiac index, as they were reported in multiple studies. We analysed these outcomes by the same method as all other outcomes.

We have made minor changes to our statistical analysis to be in line with current Cochrane standards. We now use mean difference instead of standardized mean difference for continuous outcomes. We now use risk ratio instead of risk difference for dichotomous outcomes. We have also employed the random-effects model where heterogeneity was detected by an I² value greater than 30%.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Baraka 1994

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Lebanon
Language: English
Single centre
Inclusion criteria: consenting adult men undergoing transurethral resection of the prostate under spinal anaesthesia
Exclusion criteria: ASA IV
Number eligible: not specified
Number enrolled: 33 (HS 17; NS 16)
Number completed study: 33

Age: not reported

Gender: men only

Interventions

Hypertonic saline group
IV solution: 3% HS
Dose: 7 ml/kg
Duration: before spinal anaesthesia
Isotonic salt solution group
IV solution: NS
Dose: 7 ml/kg
Duration: before spinal anaesthesia
Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesPeak serum sodium
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "Patients were allocated randomly to two groups."

Not described

Allocation concealment (selection bias)Unclear risk

Quote: "Patients were allocated randomly to two groups."

Not described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Outcomes are reported for all enrolled participants

We note a discrepancy between the number of participants enrolled to hypertonic saline described in the text (n = 17) and the number reported in table 1 (n = 19). It is our assessment that, given the age of this publication, the error is typographical

Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Bruegger 2005

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: no
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Germany
Language: English
Single centre
Inclusion criteria: people undergoing elective infrarenal aortic aneurysm repair
Exclusion criteria: ASA IV; renal dysfunction; congestive heart failure; recent brain infarction; contra-indication to starch or dextran. Intraoperative exclusion criteria were suprarenal clamping and aortic
aneurysm that extended into the iliac arteries
Number eligible: Not specified
Number enrolled: 28 (HS 14; NS 14)
Number completed study: 28

Age: not reported

Gender: men 25, women 3

Interventions

Hypertonic saline group
IV solution: 7.5% NaCl
Dose: 250 ml

Isotonic salt solution group
IV solution: NS
Dose: 250 ml

Co-interventions: dextran 70 given with HS; hydroxyethyl starch given with NS
Co-interventions applied differentially between groups: No

Study period: duration of surgery plus 72 hours

OutcomesFluid volume transfused
Blood transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
NotesDifferent colloids given to experimental and control groups. Study included because the effect of the different colloids is equivalent. The study was designed to test a commercially available hypertonic salt-colloid combination with an isotonic salt-colloid comparison
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "The patients were randomly assigned"

Sequence generation is not described

Allocation concealment (selection bias)Unclear risk

Quote: "The patients were randomly assigned"

Allocation concealment is not described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes are reported for all enrolled patients
Selective reporting (reporting bias)Unclear risk

Quote: "We studied 28 patients (three female)"

We note the disproportionately low number of women enrolled in the study but there is insufficient evidence to prove bias

There is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported

Other biasLow riskNo other sources of bias identified

Cross 1989

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: USA
Language: English
Inclusion criteria: consenting people undergoing coronary artery bypass
Exclusion criteria: cardiac arrhythmia; cardiac, pulmonary, renal, hepatic failure
Number eligible: not given
Number enrolled: 20 (HS 11; ISS 9)
Number completed study: 20

Age: not reported

Gender: men 19, women 1

Interventions

Hypertonic saline group
IV solution: HS (1.8%, 304 meq Na/L)
Dose: 100 cc/hour
Duration: Postoperative admission to ICU for 24 hours
Subsequent maintenance: D5/0.45NaCl if serum sodium > 155 meq/L

Isotonic salt solution group
IV solution: NS
Dose: 100 cc/hour
Duration: admission to ICU for 24 hours
Postoperative maintenance: D5/0.45NaCl if serum sodium > 155 meq/L

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: 24 hours from the beginning of surgery

OutcomesLOS hospital
LOS ICU
Fluid volume transfused
Blood transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "Patients were randomly assigned", "the code was not broken"

The sequence generation is not described. Randomization was probably performed

Allocation concealment (selection bias)Low risk

Quote: "Patients were randomly assigned", "the code was not broken"

A code was used to conceal allocation

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote: "Physicians and nurses directly involved in patient care did not know the identity of the solution"

Likely as stated

Blinding of outcome assessment (detection bias)
All outcomes
Low risk

Quote: "Physicians and nurses directly involved in patient care did not know the identity of the solution", "the code was not broken until after the end of the study"

Likely as stated

Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes are reported for all participants enrolled in the study
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Durasnel 1999

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Niger
Language: French
Single centre
Inclusion criteria: consenting adults undergoing surgery using spinal anaesthesia
Exclusion criteria: systemic infection, coagulopathy, allergy to local anaesthetic, uncorrected hypovolaemia, congestive heart failure, kidney failure
Number eligible: not specified
Number enrolled: 50 (HS 25; ISS 25)
Number completed study: 48 (1 from each group excluded, cause not given)

Age: not reported

Gender: men 39, women 9

Interventions

Hypertonic saline group
IV solution: 7.5% HS
Dose: 100 ml
Duration: prior to anaesthesia

Isotonic salt solution group
IV solution: 0.9% NaCl
Dose: 100 ml
Duration: prior to anaesthesia

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesHaemodynamic parameters
Fluid volume transfused
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "prospective, randomized, double-blinded study"

Not described

Allocation concealment (selection bias)Unclear risk

Quote: "prospective, randomized, double-blinded study"

Not described

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: "prospective, randomized, double-blinded study"

Not described

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk

Quote: "prospective, randomized, double-blinded study"

Not described

Incomplete outcome data (attrition bias)
All outcomes
High risk50 participants were enrolled but 1 from each group was removed without explanation
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Ishikawa 1996

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: no (1 participant in RL group excluded during study)
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Japan
Language: Japanese
Inclusion criteria: People undergoing lower limb or pelvic surgery with epidural anaesthesia
Exclusion criteria: ASA classification II, III or IV; MAP decrease by 50 mm Hg
Number eligible: 24
Number enrolled: 24
Number completed study: 24

Relevant data available on: 15 (HS 8; IS 7)

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: 7.2% HS
Dose: 1.8 ml/kg
Duration: 20 minutes
Postoperative maintenance: ISS

Isotonic salt solution group
IV solution: NS
Dose: 1 - 2 ml/kg/hr
Duration: study period

Co-interventions: epidural anaesthesia
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesPeak serum sodium
Haemodynamic parameters
Funding sourceNot described
NotesTranslations supplied by Dr Hideaki Tanaka and Dr Yoshihisa Morita
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Blinding of outcome assessment (detection bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Incomplete outcome data (attrition bias)
All outcomes
High riskReasons for enrolled participants not completing the study not reported
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Jarvela 2000

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Finland
Language: English
Single centre
Inclusion criteria: consenting fit people having lower limb surgery under spinal anaesthesia
Exclusion criteria: ASA III or IV
Number eligible: not specified
Number enrolled: 40 (HS 20; ISS 20)
Number completed study: 40

Age: not reported

Gender: men 30, women 10

Interventions

Hypertonic saline group
IV solution: 7.5% HS
Dose: 4 ml/kg
Duration: 30 minute
Postoperative maintenance: D5 / 0.3% NaCl at 1 ml/kg/hour

Isotonic salt solution group
IV solution: NS
Dose: 4 ml/kg
Duration: 30 minute
Post-operative maintenance: D5/0.3% NaCl at 1 ml/kg/hour

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery and post-anaesthetic recovery period

OutcomesFluid volume transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "randomized, double-blinded study"

Not described

Allocation concealment (selection bias)Low risk

Quote: "randomized, double-blinded study"

Assessed following communication with the study author

Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: "randomized, double-blinded study"

Not described

Blinding of outcome assessment (detection bias)
All outcomes
Unclear risk

Quote: "randomized, double-blinded study"

Not described

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Jarvela 2001

Methods

Publication type: full article

Study type: RCT

Baseline comparison: yes

Baseline similarity: yes

Control of co-interventions: yes

Completeness of follow-up: yes

Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Finland
Language: English
Single centre
Inclusion criteria: People undergoing elective coronary artery bypass graft
Exclusion criteria: not specified
Number eligible: not specified
Number enrolled: 72 (HS 36; ISS 36)
Number completed study: 72

Age: not reported

Gender: men 59, women 13

Interventions

Hypertonic saline group
IV solution: 7.5% HS
Dose: 4 ml/kg
Duration: 30 minutes
Postoperative maintenance: D5/0.3% NaCl at 1 ml/kg/hour

Isotonic salt solution group
IV solution: NS
Dose: 4 ml/kg
Duration: 30 minutes
Postoperative maintenance: D5/0.3% NaCl at 1 ml/kg/hour

Co-interventions: 4% albumin to maintain cardiac index at 2.5 L/min/m³
Co-interventions applied differentially between groups: no

Study period: duration of surgery and postoperative period until next morning

OutcomesFluid volume transfused
Weight gain
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Extubation times
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "randomly allocated according to a list of random digits"

Random-digit table

Allocation concealment (selection bias)Low riskAssessed following communication with the study author
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Quote from correspondence: "Patients, investigators and outcome assessors were not blinded".

Not performed.

Blinding of outcome assessment (detection bias)
All outcomes
High risk

Quote from correspondence: "Patients, investigators and outcome assessors were not blinded"

Not performed

Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Kato 1996

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Japan
Language: English
Inclusion criteria: consenting people undergoing transurethral resection of the prostate
Exclusion criteria: not given
Number eligible: not given
Number enrolled: 40 (HS 20; ISS 20)
Number completed study: 40

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: 3% HS
Dose: 4 ml/kg/min
Duration: adjusted to maintain mean arterial pressure at 80% of preoperative value

Isotonic salt solution group
IV solution: RL
Dose: 4 ml/kg/min
Duration: adjusted to maintain mean arterial pressure at 80% of preoperative value
Postoperative maintenance:

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery plus first postoperative day

OutcomesFluid volume transfused
Peak serum sodium
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Low riskParticipants, investigators and outcome assessors were blinded
Blinding of outcome assessment (detection bias)
All outcomes
Low riskParticipants, investigators and outcome assessors were blinded
Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskClinically relevant outcomes are defined and reported.There is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Kimura 1994

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: unclear

Study dates: not reported

Participants

Country: Japan
Language: Japanese
Inclusion criteria: people undergoing transurethral resection of the prostate, spinal anaesthesia
Exclusion criteria: ASA III, IV; hypertension; diabetes; endocrine disease
Number eligible: 14
Number enrolled: 14 (HS 7; ISS 7)
Number completed study: 14

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: HS (213 meq Na / L)
Dose: 8 ml/kg/hour for 1st hour; 4 ml/kg/hour for 2nd hour; 2 ml/kg/hour for 3rd hour

Isotonic salt solution group
IV solution: RL
Dose: 8 ml/kg/hour for 1st hour; 4 ml/kg/hour for 2nd hour; 2 ml/kg/hour for 3rd hour

Co-interventions: spinal anaesthesia
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesPeak serum sodium
Haemodynamic parameters
Plasma aldosterone, ADH
Funding sourceNot described
NotesTranslation provided by Dr Hideaki Tanaka and Dr Yoshihisa Morita
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Kølsen-Petersen 2004

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: December 2001 - January 2003

Participants

Country: Denmark
Language: English
Inclusion criteria: adult women undergoing elective hysterectomy
Exclusion criteria: ASA III or IV; cardiac failure; renal failure; anaemia; diabetes mellitus; certain medications that effect the immune response
Number eligible: 192 screened
Number enrolled: 62 (HS 21; NS-4 21; NS-32 20)
Number completed study: 58 (1 HS participant withdrew consent; 1 HS had anaphylactoid reaction to anaesthetic agent; 1 NS-4 participant transferred to another hospital; 1 NS-32 participant returned to the operating room for haemorrhage)

Study data used: HS (19) and NS-4 (20).

Age: 32 - 53

Gender: women only

Interventions

Hypertonic saline group
IV solution: 7.5% NaCl
Dose: 4 ml/kg
Duration: over 10 minutes before hysterectomy
Postoperative maintenance: not specified

Isotonic salt solution group
IV solution: NS
Dose - 2 groups: 'NS-4' received 4 ml/kg; 'NS-32' received 32 ml/kg
Duration: over 10 minutes before hysterectomy
Postoperative maintenance: not specified

Co-interventions: anaesthesia, analgesia
Co-interventions applied differentially between groups: no

Study period: duration of surgery plus 48 hours after closure of the wound

OutcomesPeak serum sodium
Urine output
Immunological parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "prospective, randomized, double-blind study"

Randomly assorted envelopes used for study arm selection

Allocation concealment (selection bias)Low risk

Quote: "The study-group assignments were placed in sealed, opaque, randomly assorted envelopes, which were opened by a hospital staff member who was not one of the study investigators"

Concealment is adequate

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote: "The study fluid was subsequently hidden in an opaque box and connected to the i.v. line in such a way that neither the patient nor the investigator was aware of the nature of the fluid"

Participants and personnel adequately blinded

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessment is adequately blinded
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Quote: "Four patients were excluded from the final analysis. One patient (HS group)
did not wish to finish the study..."

Reasons for missing outcomes are reported and balanced across groups

Selective reporting (reporting bias)Unclear riskClinically relevant outcomes are defined and reported.There is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Lavu 2014

Methods

Publication type: full article

Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: May 2011 - November 2013

Participants

Country: United States
English
Inclusion criteria: People undergoing pancreaticoduodenectomy
Exclusion criteria: metabolic acidosis, active sepsis or bacteraemia, congestive heart failure, chronic renal insufficiency, pregnancy, sickle-cell anaemia, hyponatraemia (serum sodium <120 mmol/L), hypernatraemia
(serum sodium >150 mmol/L), morbid obesity (body mass index >50), and extension of surgery to total pancreatectomy,unresectable disease or distant metastasis.
Number eligible: 259
Number enrolled: 264 (LR 132, HS 132; 4 from LR became ineligible (2 unresectable, 2 total pancreatectomies), 1 from HS became ineligible (1 total pancreatectomy))
Number completed study: 259 (HS 131, LR 128)

Age: 25 - 91

Gender: men 54%, women 46%

Interventions

Lactated Ringer's group
IV solution: lactated Ringer's
Dose: 15 mL/kg/hr during the operation, with blood loss replaced in a 3:1 ratio. Then at a rate of 2 mL/kg/hr.
Duration: Until 8 AM POD 1.

Hypertonic saline group
IV solution: 1 mL/kg/hr of HYS (3.0% NaCl) and 9 mL/kg/hr of LR
Dose: a 1 mL/kg bolus of HYS for more than 15 minutes on randomization, and then they were continued on 1 mL/kg/hr of HYS and 9 mL/kg/hr of LR for a total infused volume rate of 10 mL/kg/hr during the operation. Blood loss was replaced at a 1:1 ratio with LR. Maintained on HYS alone at a rate of 1 mL/kg/hr
Duration: until 8 AM on the morning of POD 1.

Co-interventions: None
Co-interventions applied differentially between groups: NA

Study period: 90 days.

Outcomes

90-day mortality

Postoperative complication rate

Total number of complications
Intraoperative estimated blood loss

Number of required fluid boluses

Postoperative hospital LOS

Readmission rate

Peri-operative mortality

Funding sourceNot described
NotesPrimary author was contacted for additional data. Author provided mean and standard deviation values for published results
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low risk

Quote: "computer-generated random permuted blocks with a 1:1 allocation (blocks of 6) (investigators were blinded to block size during study accrual)"

Computer randomized allocation

Allocation concealment (selection bias)Low risk

Quote: "administrator would open in sequence, a numbered, opaque envelope containing the assignment"

Assignment in opaque numbered envelope and provided at the time of surgery by a third-party administrator

Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote: "surgeons and anaesthesia staff blinded to the process until the assignment was revealed"

Participants and personnel were blinded to allocation

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were likely unaware of treatment allocation
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Quote: "Five patients were excluded from the analysis after accrual due to unresectability..."

Reasons for missing outcomes are reported and balanced across groups

Selective reporting (reporting bias)Low riskClinically relevant outcomes are identified and reported
Other biasLow riskNo other source of bias identified

Leverve 2008

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: no (22 had to be excluded due to major protocol violation or incomplete data collection)
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Indonesia
Language: English
Inclusion criteria: men or women, 18–75 years, in postoperative period in ICU post-CABG surgery, either on-pump or off-pump, and requiring postoperative fluid resuscitation
Exclusion criteria: people having undergone combined operations, those needing an intra-aortic balloon pump, severe arrhythmia (ventricular tachycardia, atrial flutter with rapid response, heart block), severe haemodynamic imbalance, severe bleeding and/or re-operation, liver dysfunction (SGOT and SGPT more than twice normal value) and renal failure (creatinine more than 20 mg L-1)
Number eligible: 230
Number enrolled: 230
Number completed study: 208 (HL 109; RL 99)

Age: 54 - 57

Gender: men 198, women 10

Interventions

Hypertonic saline group
IV solution: HL (504.15 mmol L-1)
Dose: titrated to maintain CVP between 8 and 12 mm Hg
Duration: during operation
Postoperative maintenance:

Isotonic salt solution group
IV solution: RL (Na = 130.5 mmol L-1)
Dose: titrated to maintain PAOP between 11 and 15 mm Hg
Duration: during operation
Postoperative maintenance:

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: 12 hours post-surgery

Outcomes

Fluid volume transfused
Fluid balance
Peak serum sodium
Urine output

MAP

Cardiac index

Funding sourceNot described
Notes12-hour data only available; urine output, MAP and CI determined from graphs.
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear risk

Quote: "Patients were randomly assigned immediately after CABG surgery"

Participants were blinded. It is unknown if personnel were blinded

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low risk

Quote: "From the 230 patients enrolled in this study, 22 had to be excluded due to major protocol violation or incomplete data collection, but they were included in the safety evaluation"

Reasons for missing outcomes are reported and balanced across groups

Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Shackford 1983

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: USA
Language: English
Inclusion criteria: people undergoing aortic surgery
Exclusion criteria: not specified
Number eligible: 61
Number enrolled: 58 (HS 30; ISS 28)
Number completed study: 58

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: HSL (250 meq Na/L)
Dose: titrated to maintain CVP within 3 torr of preoperative value
Duration: during operation
Postoperative maintenance: D5/0.25 NaCl

Isotonic salt solution group
IV solution: RL
Dose: titrated to maintain CVP within 3 torr of preoperative value
Duration: during operation
Postoperative maintenance: D5/0.25 NaCl

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of hospital stay for surgery

OutcomesFluid volume transfused
Blood transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Blinding of outcome assessment (detection bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Shackford 1987

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Blinding of care givers: no
Additional features to blind fluid administered: no
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: USA
Language: English
Inclusion criteria: People undergoing aortic aneurysm repair or aorto-bifemoral bypass
Exclusion criteria: not specified
Number eligible: 52
Number enrolled: 52 (HS 26; ISS 26)
Number completed study: 52

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: HSL (250 meq Na/L)
Dose: titrated to maintain CVP within 3 torr of preoperative value
Duration: during operation
Postoperative maintenance: D5/0.25 NaCl

Isotonic salt solution group
IV solution: RL
Dose: titrated to maintain CVP within 3 torr of preoperative value
Duration: during operation
Postoperative maintenance: D5/0.25 NaCl

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery plus first4 postoperative days

OutcomesFluid volume transfused
Blood transfused
Fluid loss
Fluid balance
Weight change
Peak serum sodium
Urine output
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Blinding of outcome assessment (detection bias)
All outcomes
High riskParticipants, investigators and outcome assessors were not blinded
Incomplete outcome data (attrition bias)
All outcomes
Low riskReasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Shao 2013

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Blinding of care givers: not defined
Additional features to blind fluid administered: not defined
Control of co-interventions: yes
Completeness of follow-up: complete
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: China
Language: English
Inclusion criteria: ASA I - II patients scheduled for elective neurosurgical procedures
Exclusion criteria: The exclusion criteria were age, less than18 years or greater than 80 years; clinical signs of significantly increased ICP such as severe headache, blurred vision and/or papilledema; history of cardiac, pulmonary and renal dysfunction; fluid or electrolyte disturbances; preoperative coagulation disorders; and preoperative treatment with diuretics and/or osmotic agents
Number eligible: 40
Number enrolled: 40
Number completed study: 40 (HS-HES 20; HES 20)

Age: 27 - 53

Gender: men 21, women 19

Interventions

Hypertonic saline group
IV solution: 250 mL of a 7.2% HS - 6% HES
Dose: 250 mL
Duration: intraoperative infusion

Isotonic salt solution group
IV solution: 6% HES
Dose: 1000 mL

Duration: intraoperative infusion

Co-interventions: Ringer's lactated solution to maintain CVP at 8 - 12 mm Hg and the MAP at greater than 65 mm Hg. 250 mL 20% mannitol
Co-interventions applied differentially between groups: no

Study period: duration of surgery

Outcomes

Volume of Ringer’s solution

Volume of PRBC infused

Intraoperative total urine output
Blood loss

Operative duration

Intraoperative bleeding severity score

Dural tension score

Fluid balance

Haemodynamic parameters

Laboratory parameters

Funding sourceNot described
NotesAuthor was contacted for further information but did not respond
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Low riskOperative team made aware of treatment at time of operation
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Quote: "after the induction of anaesthesia, the patients were randomly assigned"

Participants are blinded to treatment. Personnel are not blinded to treatment

Blinding of outcome assessment (detection bias)
All outcomes
High risk

Not described

Outcome assessors are probably not blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo incomplete data identified
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNone identified

Veroli 1992

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: France
Language: English
Inclusion criteria: consenting people having lower limb surgery with lumbar extradural anaesthesia
Exclusion criteria: not specified
Number eligible: not specified
Number enrolled: 30 (HS 10; RL 10; NS 10)
Number completed study: 30

Age: 26 - 65

Gender: men 15, women 15

Interventions

Hypertonic saline group
IV solution: HS 5%
Dose: 2.3 ml.kg
Duration: preoperative bolus

Isotonic salt solution group
IV solution: RL or NS
Dose: 15 ml RL/kg or 13 ml NS/kg
Duration: preoperative bolus

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesFluid volume transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear risk

Quote: "prospective double-blinded study"

Not described

Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote: "patients were transferred to the operating theatre and were cared for by a physician (P.V.) blinded to the fluid preload administered previously"

Participants and personnel blinded to treatment

Blinding of outcome assessment (detection bias)
All outcomes
Low riskOutcome assessors were blinded to treatment
Incomplete outcome data (attrition bias)
All outcomes
Low riskOutcomes reported for all participants enrolled. Reasons for missing outcomes are reported and balanced across groups
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Wang 1997

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Blinding of care givers: unclear
Additional features to blind fluid administered: no
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: China
Language: English
Single centre
Inclusion criteria: consenting fit people having herniorrhaphy under spinal anaesthesia
Exclusion criteria: ASA II, III or IV
Number eligible: not specified
Number enrolled: 60 (HS 30; ISS 30)
Number completed study: 60

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: 3% HS
Dose: 7 ml/kg
Duration: bolus before surgery

Isotonic salt solution group
IV solution: 0.9% NaCl
Dose: 7 ml/kg
Duration: bolus before surgery

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesHypotension
Peak serum sodium
Haemodynamic parameters
Funding sourceNot described
Notes 
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcomes detected
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Younes 1988

  1. a

    ASA: American Society Anesthesiology classification
    CABG: coronary artery bypass graft
    CVP: central venous pressure
    D5/0.45NS: dextrose 5% in 0.45% saline
    HS: hypertonic saline
    HSL: hypertonic saline lactate
    ICU: intensive care unit
    IS: isotonic saline
    ISS: isotonic salt solution
    IV: intravenous
    LOS: length of stay
    MAP: mean arterial pressure
    NS: normal saline (154 meq Na per litre)
    PAOP: pulmonary artery occlusion pressure
    POD: postoperative day
    PRBC: packed red blood cells
    RCT: randomized control trial
    RL: Ringer's Lactate (130 meq Na per litre)
    SGOT: serum glutamic oxaloacetic transaminase
    SGPT: serum glutamate pyruvate transaminase

Methods

Publication type: full article
Study type: RCT
Baseline comparison: yes
Baseline similarity: yes
Blinding of care givers: unclear
Additional features to blind fluid administered: no
Control of co-interventions: yes
Completeness of follow-up: yes
Intention-to-treat analysis: yes

Study dates: not reported

Participants

Country: Brazil
Language: Portuguese
Single centre
Inclusion criteria: Adults undergoing aortic aneurysm repair or aortobifemoral bypass
Exclusion criteria: not given
Number eligible: not given
Number enrolled: 31 (HS 18; ISS 13)
Number completed study: 31

Age: not reported

Gender: not reported

Interventions

Hypertonic saline group
IV solution: 7.5% HS
Dose: 4 ml/kg
Duration: 15 minute bolus
Postoperative maintenance: ISS to maintain CVP and MAP within 10% of starting value

Isotonic salt solution group
IV solution: 0.9% NaCl
Dose: 4 ml/kg
Duration: 15-minute bolus
Postoperative maintenance: ISS to maintain CVP and MAP within 10% of starting value

Co-interventions:
Co-interventions applied differentially between groups: no

Study period: duration of surgery

OutcomesLOS hospital
LOS ICU
Fluid volume transfused
Blood transfused
Fluid loss
Fluid balance
Peak serum sodium
Urine output
Haemodynamic parameters
Funding sourceNot described
NotesTranslation provided by Ms. Christiane Baldwin
Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNot described
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcomes detected
Selective reporting (reporting bias)Unclear riskThere is no explicit reference to participant survival. Other clinically relevant outcomes that fit the trial design are reported
Other biasLow riskNo other sources of bias identified

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Auler 1987Consecutive participants enrolled. Study not randomized
Auler 1992Study of intraoperative respiratory physiology but did not measure outcomes such as weight gain, fluid balance or peak serum sodium or determine postoperative survival
Li 2014No comparison to IS
Li 2015No comparison to IS
Shao 2005Dr Shao kindly responded to an email query on November 30, 2006: "I performed this project non-randomly, allocated distinct groups on the basis of different diseases and operation methods, but single-blinded (for patients)"
Yang Z 2014No outcomes of interest reported
Yousefshahi F 2013No measured outcomes were relevant to this review. Authors were contacted for additional information but did not respond

Ancillary