Cuidado cardiaco rápido para pacientes adultos sometidos a cirugía cardíaca
Referencias
References to studies included in this review
References to studies excluded from this review
Additional references
References to other published versions of this review
Characteristics of studies
Characteristics of included studies [ordered by study ID]
Ir a:
| Methods | Parallel‐group randomized controlled trial, conducted in England. Study dates not reported | |
| Participants | 39 elective cardiac (coronary artery and/or valve) surgical patients with low cardiac output (defined as cardiac index < 2.5 L/min/m2 and a minimal pulmonary capillary wedge pressure of 7 mmHg) without hepatic or renal impairment | |
| Interventions | Low‐dose opioid, early extubation (fentanyl 15 μg/kg and propofol, extubated within 8 hours) in 20 participants High‐dose opioid, usual care (fentanyl 60 μg/kg and midazolam, extubated after more than 8 hours) in 19 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Time to extubation Length of stay in the ICU | |
| Notes | Median time to extubation and length of stay in the intensive care unit were reported with no interquartile range, thus data were not used in the meta‐analysis. Study authors did not report mortality outcomes or postoperative complications. No power calculation was done. Funding source was J.F. Blades and Zeneca Pharma, Wilmslow, Cheshire. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawal from the study during follow‐up |
| Selective reporting (reporting bias) | High risk | Study authors did not report mortality outcomes or postoperative complications. |
| Other bias | Low risk | Baseline participant characteristics (age, sex, weight, surface area, duration of surgery, type of surgery) were comparable. |
| Methods | Parallel‐group blinded randomized controlled trial, conducted in the United Kingdom. Study dates not reported | |
| Participants | 98 elective coronary artery bypass graft (CABG) patients, with no ECG abnormalities, not older than 71 years, with no digitalis therapy, no left or right bundle branch block, no morbid obesity (BMI > 35), with FEV1 or FVC > 50%, no poor left ventricular function. Patients were excluded from the study after surgery if they failed to meet the following criteria: haemodynamically stable; blood loss < 120 mL/h and arterial PO2 ≤ 7 kPa with an inspired oxygen concentration of 50%; and PEEP ≤ 5 cm H2O. Patients with < 10 hours of acceptable number of beats in the postbypass period and with abnormal QRS complexes (i.e. not artefact, ventricular ectopics or bundle branch block) were excluded from the ECG analysis. | |
| Interventions | Low‐dose opioid, early extubation (within 8 hours) in 50 participants, but ECG analysis complete in 43 participants. Anaesthesia with fentanyl 15 μg/kg and isoflurane HIgh‐dose opioid, usual care (more than 8 hours) in 48 participants, but ECG analysis complete in 42 participants. Anaesthesia with fentanyl 50 μg/kg and isoflurane Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Time to extubation Risk of major bleeding Hospital length of stay Length of stay in the ICU | |
| Notes | Of 50 participants in the early extubation group, 3 failed early extubation in the designated period of 8 hours. Of 50 participants in the early extubation group, 2 had "excess blood loss (≥ 120 mL/h)". Power calculation was done. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "On arrival in the operating room, patients were allocated to enter early extubation (group E) or late extubation (group L) according to a prepared randomization schedule" |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | Assessors were blinded to the diagnosis of myocardial ischaemic outcomes. |
| Incomplete outcome data (attrition bias) | Low risk | Reasons and details for 13 dropouts were given. These data were excluded from further analysis. |
| Selective reporting (reporting bias) | Low risk | Reported all collected outcomes |
| Other bias | Low risk | Used multi‐variate analysis to examine ST depression to adjust for hypertension imbalance between 2 groups. All other participant characteristics and intraoperative surgical details were similar between groups. |
| Methods | Parallel‐group randomized controlled trial, conducted in Taiwan. Study dates not reported | |
| Participants | 50 patients undergoing elective off‐pump coronary artery bypass graft surgery. Patients were excluded if they had severe ventilatory impairment, history of renal failure, diabetes mellitus or American Society of Anesthesiologists' physical status of IV or above, or had undergone a previous cardiac surgical procedure. | |
| Interventions | Low‐dose opioid anaesthesia in 25 participants (isoflurane‐based anaesthesia with mean fentanyl 2.9 ± 0.2 μg/kg) High‐dose opioid anaesthesia in 25 participants (fentanyl‐propofol‐based anaesthesia with mean fentanyl 21.8 ± 2.7 μg/kg) Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Time to extubation Length of stay in ICU | |
| Notes | No power calculation was done. Funding was provided by a grant from Tri‐Service General Hospital (grant number: TSGH‐C92‐81). Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawal from the study during follow‐up |
| Selective reporting (reporting bias) | Low risk | Reported all collected outcomes |
| Other bias | Low risk | Baseline participant characteristics (age, sex, height, weight, duration of anaesthesia, ejection fraction) were comparable. |
| Methods | Parallel‐group double‐blinded randomized controlled trial, conducted in Canada. Study conducted from May 1992 to May 1994 | |
| Participants | 120 elective primary coronary artery bypass graft patients younger than 75 years of age, with LV function grades I to IV, no previous cardiac surgery, no allergy to propofol, no left bundle branch block or digitalis therapy, no documented myocardial infarction within previous 3 weeks, no active congestive cardiac failure, no inotropic therapy within 24 hours of surgery, no current intra‐aortic balloon pump, no severe hepatic disease, no renal insufficiency, no severe chronic obstructive pulmonary disease, no history of stroke or seizure | |
| Interventions | Low‐dose opioid, early extubation group: fentanyl 15 μg/kg, isoflurane and propofol anaesthesia with extubation 1 to 6 hours after surgery in 60 participants HIgh‐dose opioid, usual care group: fentanyl 50 μg/kg, isoflurane and midazolam anaesthesia with extubation on the day after surgery in 60 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Risk of mortality in hospital Risk of mortality at 1 year Risk of tracheal reintubation Risk of myocardial infarction (defined as either or both of the following findings: CK‐MB levels > 50 IU/L and representing > 8% of total CK or major 12‐lead ECG changes (including new Q‐wave > 0.04 seconds in duration and > 1 mm in depth, ST‐segment elevation or depression > 2 mm lasting 48 hours and a symmetrical T‐wave inversion persisting for 48 hours) from baseline in ≥ 2 leads) Risk of major bleeding Risk of stroke (defined as sudden onset of focal neurological deficit, symptoms of focal neurological deficit persisting > 24 hours, or both, as documented by a neurologist) Risk of renal failure (requiring dialysis or haemofiltration) Time to extubation Length of stay in the ICU Length of stay in hospital | |
| Notes | Departmental actual cost savings in uncomplicated CABG surgery used for analysis (1996b, Table 9), converted to USD 2015 values. No power calculation done. Study was supported, in part, by a grant from Anesthesia Patient Safety Foundation, American Society of Anesthesiologists, 1995; a 1995 Investigator Award from the Society of Cardiovascular Anesthesiologists granted to first study author; and a grant from Zeneca Pharma, Canada, to second study author for the ICU sedation medication cost analysis. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Patients were randomly and consecutively allocated according to a computer‐generated randomization code to early (study) or conventional (control) groups" |
| Allocation concealment (selection bias) | Low risk | "Concealed in an envelope until anaesthesia was induced" |
| Blinding (performance bias and detection bias) | Low risk | "The surgeon and the research assistant collecting the data, but not the anaesthesiologist providing the clinical care, were blinded to the group assignments". Radiologist was blinded to study group assignment. |
| Incomplete outcome data (attrition bias) | Low risk | Nine participants in each group did not meet extubation criteria within the defined period. |
| Selective reporting (reporting bias) | Low risk | All collected outcomes reported |
| Other bias | Low risk | "There were no differences in demographic data, including the distribution of left ventricular function, between the early and conventional group" |
| Methods | Parallel‐group randomized controlled trial, conducted in Canada. Study conducted from October 1995 to September 1996 | |
| Participants | 48 elective coronary artery bypass surgery patients who were younger than 75 years old, French speaking, living within a 60‐ to 70‐km radius of the hospital. Exclusion of those with “psychologic or psychiatric antecedents; prescription of lithium and/or antidepressant medication; alcohol abuse; chronic renal failure; ejection fraction less than 30%; valvuloplasty; significant peripheral vascular disease; uncontrolled hypertension; chronic obstructive pulmonary disease; and combined surgeries” | |
| Interventions | Early extubation (< 8 hours after surgery) in 22 participants Usual care (8 to 24 hours after surgery) in 25 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of stroke Time to extubation | |
| Notes | This study focused on postoperative cognitive dysfunction. Time to extubation was defined as "delay between arrival at the intensive care unit and the start of withdrawal from anaesthetic/analgesic agents". Weaning protocol was the same in both groups, but timing was different, as described in the paper. No power calculation was done. Study was supported, in part, by the Department of Anesthesia, Faculty of Medicine, University of Montreal, Canada. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "Patients were randomly assigned to one of two groups" |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | Reasons for withdrawals given |
| Selective reporting (reporting bias) | Low risk | All collected outcomes reported |
| Other bias | High risk | Most demographics, co‐morbidities and surgical data were similar between groups. However, early extubation groups were 6 years younger than conventional extubation groups and had lower prevalence of carotid bruit. |
| Methods | Parallel‐group randomized controlled trial, conducted in the United States. Study dates not reported | |
| Participants | 70 patients undergoing primary coronary artery bypass surgery. Excluded were those with concomitant valve, carotid artery or other co‐incident surgery. | |
| Interventions | Low‐dose opioid (isoflurane anaesthesia with a continuous infusion of propofol and mean fentanyl dose 13.7 μg/kg) in 35 participants High‐dose opioid (isoflurane anaesthesia and mean fentanyl dose 21.0 μg/kg) in 35 participants Details of who decided when to extubate were not given in the paper. | |
| Outcomes | Risk of mortality in hospital Risk of myocardial infarction Risk of stroke Risk of tracheal reintubation Time to extubation Length of stay in the ICU Length of stay in hospital Cost of anaesthesia drugs | |
| Notes | Weaning protocol was the same in both groups, but timing was different, as described in the paper. Power calculation was performed. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Patients were randomized by a computer‐generated scheme" |
| Allocation concealment (selection bias) | High risk | "..and the anaesthesia provider was informed of the assignment while preparing the room for anaesthesia" |
| Blinding (performance bias and detection bias) | Unclear risk | "..and the anaesthesia provider was informed of the assignment while preparing the room for anaesthesia" |
| Incomplete outcome data (attrition bias) | Low risk | No participants withdrew from the study. |
| Selective reporting (reporting bias) | Low risk | All collected outcomes reported |
| Other bias | Low risk | "Patients were very similar in baseline demographics (Table 1), although anaesthesia and cardiopulmonary bypass times were slightly longer in the propofol group" |
| Methods | Parallel‐group randomized controlled trial, conducted in Hong Kong. Study dates not reported | |
| Participants | 50 adults undergoing elective coronary artery bypass graft (CABG). Excluded were patients with LV ejection fraction > 30%, concomitant vascular or aortic surgery, older than 80 years, chronic pulmonary artery disease requiring bronchodilator therapy, significant hepatic disease (alanine aminotransferase or aspartate aminotransferase > 150 U/L), renal failure or history of seizure and stroke | |
| Interventions | Early extubation (within 6 hours using adaptive‐support ventilation) in 23 participants Usual care (after 7 hours with pressure‐regulated volume‐controlled ventilation with auto‐mode) in 25 participants Details of who decided when to extubate were not given in the paper. | |
| Outcomes | Risk of mortality in hospital Time to extubation Length of stay in the ICU Risk of stroke Risk of major bleeding Risk of tracheal reintubation Risk of acute renal failure (defined as new requirement for renal replacement) | |
| Notes | Anaesthesia (low‐dose fentanyl and midazolam, with propofol or sevoflurane) in both groups was the same. Details of weaning protocol were given in the paper. Same weaning protocol was given to both groups, but timing was different. Power calculation was performed. Funding source was the department. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization sequence was computer‐generated. |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | High risk | "This was an unblinded randomized controlled trial" |
| Incomplete outcome data (attrition bias) | Low risk | Reasons for withdrawal given |
| Selective reporting (reporting bias) | Low risk | All outcomes collected were reported. |
| Other bias | Low risk | Participant demographics, anaesthesia and surgical procedures were similar between groups. However, participants in the intervention group had lower LVEF and higher EuroSCORE compared with participants in the control group. |
| Methods | Parallel‐group randomized controlled trial, conducted in Japan. Study dates not reported | |
| Participants | 180 elective coronary artery bypass graft (CABG) patients with no history of cerebrovascular disease, diabetes, psychiatric illness, renal disease or active liver disease. Patients were excluded if they had moderate or severe atherosclerotic lesions in the ascending aorta or carotid artery stenosis confirmed by preoperative ultrasonography and magnetic resonance imaging. | |
| Interventions | Low‐dose opioid (propofol infusion) in 90 participants High‐dose opioid (fentanyl infusion, mean fentanyl 58 ± 15 μg/kg) in 90 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Risk of tracheal reintubation (for pneumonia) Risk of acute renal failure (creatinine > 3 mg/dL) Risk of stroke (defined as clinical evidence of focal cerebral infarction including hemiparesis, visual or gait disturbance, mental changes or a combination of these) Time to extubation Length of ICU stay | |
| Notes | Both groups had anaesthesia induced by midazolam 0.3 mg/kg, fentanyl 10 μg/kg and vecuronium 0.2 mg/kg. Power calculation was done. Study was supported, in part, by a grant of first study author from the Japanese Ministry of Science and Education. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | Neurological examiner was blinded to group assignment. |
| Incomplete outcome data (attrition bias) | Low risk | Participant follow‐up was complete except for neuropsychological assessments at 6 months. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected were reported. |
| Other bias | Low risk | "No significant differences in demographic data between the two groups except for phenylephrine dosage" |
| Methods | Parallel‐group randomized controlled trial, conducted in Taiwan. Study dates not reported | |
| Participants | 107 patients undergoing elective coronary artery bypass graft surgery. Patients were excluded if they had severe ventilatory impairment or history of renal failure or diabetes mellitus, or if they had undergone a previous cardiac surgical procedure. | |
| Interventions | Low‐dose opioid anaesthesia in 54 participants (isoflurane‐based anaesthesia with mean fentanyl 4.4 ± 0.2 μg/kg) High‐dose opioid anaesthesia in 53 participants (fentanyl‐midazolam‐based anaesthesia; mean fentanyl was 66.4 ± 3.2 μg/kg) Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Time to extubation Length of stay in ICU Risk of postoperative bleeding (> 100 mL/h drainage) | |
| Notes | No power calculation was done. Study was supported, in part, by a grant from Tri‐Service General Hospital (grant number: TSGH‐C90‐1). Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawal from the study during follow‐up |
| Selective reporting (reporting bias) | Low risk | Reported all collected outcomes |
| Other bias | Low risk | Baseline participant characteristics (age, sex, height, weight, duration of anaesthesia, duration of cardiopulmonary bypass, cardiac output, cardiac index, ejection fraction, aortic clamping time) were comparable. |
| Methods | Parallel 3‐arm randomized controlled trial, conducted in Oman. Study conducted from January 2004 to June 2004 | |
| Participants | 180 primary CABG patients with ejection fraction > 30% and no known hypersensitivity to opioids, IV propofol, benzodiazepines or non‐steroidal antiinflammatory drugs. Excluded patients had morbid obesity, neurological condition making pain assessment difficult to evaluate after surgery, significant arrhythmias, congestive cardiac failure, preoperative intra‐aortic balloon pump or severely impaired organ function. | |
| Interventions | Low‐dose opioid group: fentanyl (mean total dose 16.5 μg/kg) and diclofenac 75 mg suppository in 60 participants High‐dose opioid group: continuous fentanyl infusion (mean total perioperative dose 39 μg/kg) in 60 participants Details of who decided when to extubate were not given. | |
| Outcomes | Time to extubation Length of postcardiac surgical unit stay | |
| Notes | Group 3: remifentanil (1 μg/kg/min and bolus IV fentanyl 1 μg/kg) in 60 participants. Remifentanil group was not included in analysis, as this is a high‐dose opioid with a short half‐life. Participants' stay in postcardiac surgical unit was considered equivalent to stay in ICU, as participants were weaned off mechanical ventilation. All groups had the same weaning protocol. Power calculation was done. No details were provided about funding source or any declarations of conflict of interest among study authors. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Participants were randomly assigned, using a computer‐generated randomization chart, to three groups..." |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | High risk | "Open labelled" |
| Incomplete outcome data (attrition bias) | Low risk | Four participants excluded with reasons given |
| Selective reporting (reporting bias) | Low risk | All collected outcomes were reported. |
| Other bias | Low risk | Demographic and surgical data were similar between groups. |
| Methods | Parallel‐group single‐blinded randomized controlled trial, conducted in Greece. Study dates not reported | |
| Participants | 144 elective coronary artery bypass patients younger than 70 years of age, with ejection fraction ≥ 35%, New York Heart Classification Class I to III, with normal preoperative respiratory function. Excluded were those with chronic renal failure, hepatic failure or cerebral dysfunction, and those who underwent redo CABG surgery | |
| Interventions | Low‐dose opioid, early extubation (4 to 7 hours) in 72 participants. Anaesthesia included fentanyl 15 to 20 μg/kg at induction and 5 μg/kg for maintenance, followed by ICU sedation and analgesia (morphine and propofol) for 2 hours. High‐dose opioid, usual care (extubation 8 to 14 hours) in 72 participants. Anaesthesia included fentanyl 50 μg/kg at induction and 10 to 15 μg/kg for maintenance, followed by ICU sedation and analgesia (morphine and midazolam) for 6 hours. Details of who decided when to extubate were not given. | |
| Outcomes | Risk of mortality in hospital Risk of myocardial infarction (new and persistent Q waves at ECG associated with an abrupt rise in CPK, CPK‐MB and troponin values) Risk of stroke Risk of sepsis Risk of major bleeding (blood loss > 500 mL during the first 6 postoperative hours, or blood loss necessitating transfusion of > 3 red cell units during the first 12 postoperative hours) Risk of acute renal failure Risk of tracheal reintubation Time to extubation Length of hospital stay | |
| Notes | No power calculation was done. No details were provided about funding source or any declarations of conflict of interest among study authors. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | "Operative and postoperative complications were assessed blinded to the randomization of the allocation" |
| Incomplete outcome data (attrition bias) | Unclear risk | No details given |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Participant characteristics between groups were similar for gender, smoking, age, preoperative LVEF (%) and NYHA classification |
| Methods | Parallel‐group randomized controlled trial, conducted in Australia. Study dates not reported | |
| Participants | 129 elective CABG surgical patients. Excluded were those undergoing concurrent valvular surgery or considered at very high risk (clinical severity score > 9) because they were more likely to require continued sedation and longer stay in the ICU. Also excluded were those with preexisting left bundle branch block or pacemaker in situ preventing ST‐segment diagnosis of perioperative myocardial ischaemia. | |
| Interventions | Low‐dose opioid (propofol infusion and mean fentanyl 15.1 μg/kg) in 58 participants High‐dose opioid (enflurane 0.2% to 1% and mean fentanyl 31.3 μg/kg) in 66 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Risk of hospital mortality Risk of postoperative myocardial infarction (new Q waves in ≥ 2 ECG leads, as detected by an independent and blinded cardiologist and creatine kinase‐MB fraction > 5%) Time to extubation in ICU | |
| Notes | Power calculation was done. Funding was provided by research grants from the Australian and New Zealand College of Anaesthetists, and the Research Committee of the Alfred Hospital. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "We randomized patients after stratification according to the surgeon's angiographic assessment of contractility to maximize equality of both groups. Randomization was determined by a table of random numbers" |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | "ICU staff were blinded to group identity" |
| Incomplete outcome data (attrition bias) | Low risk | "...a total of 129 patients (103 male, 26 female) were enrolled in this study, with subsequent exclusion of 5 patients" |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | "The groups were well‐matched for age, clinical severity score, myocardial contractility, preinduction haemodynamics and duration of surgery. Despite stratification and randomization, there were more women in the enflurane based anaesthesia group and those in the propofol group had a longer aortic cross‐clamp time" |
| Methods | Parallel 3‐arm double‐blinded randomized controlled trial, conducted in Australia. Study dates not reported | |
| Participants | 87 elective coronary artery bypass patients younger than 75 years of age. Excluded were those with body weight > 100 kg, allergic to trial medications, at high risk of mortality, uncontrolled hypertension or hypotension, congestive cardiac failure or an ejection fraction < 25%, with atrioventricular or left bundle branch block detected on preoperative electrocardiogram or with a pacemaker in situ. | |
| Interventions | Low‐dose opioid (propofol and mean fentanyl 15 μg/kg) in 24 participants High‐dose opioid (propofol and mean fentanyl 28 μg/kg) in 24 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of postoperative myocardial infarction (new Q waves in ≥ 2 ECG leads as detected by an independent and blinded cardiologist) Risk of wound infection (unpublished) Risk of stroke Risk of acute renal failure (requiring dialysis or haemofiltration) (unpublished) Time to extubation in ICU Length of hospital stay (unpublished) Total hospital cost (OT drug cost, OT other cost, ICU total cost) | |
| Notes | Data from remifentanil (0.85 μg/kg/min) were not included as they did not fit the criteria for the early extubation group nor the conventional extubation group (as per correspondence with Prof Myles). Complete total hospital cost data were available for 46 participants (high cost outliers in 3 participants not included in analysis). Power calculation was done. First study author was supported by a National Health and Medical Research Council Practitioner Fellowship award; study was supported by the Alfred Hospital Wholetime Medical Specialists Scheme and Glaxo Wellcome. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization code was created by table of random numbers, and participants were stratified to high‐ or low‐risk groups. |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | "The clinical trial unit or hospital pharmacy department who prepared solutions according to the randomization code maintained blinding of the study drug preparations" |
| Incomplete outcome data (attrition bias) | Low risk | 87 participants were enrolled, and 10 participants were excluded (1 participant withdrew consent before surgery, 2 had their surgery deferred and 7 failed to receive their allotted study medication) |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Perioperative factors were similar between groups. |
| Methods | Parallel‐group randomized controlled trial, conducted in Canada. Study conducted from September 1997 to March 1998 | |
| Participants | 35 patients undergoing elective or semi urgent coronary artery bypass grafting surgery, aged younger than 80 years with a normal preoperative chest radiograph. Excluded were patients who underwent emergency surgery, those with significant valvular heart disease requiring surgical repair, with previous CABG or heart valve surgery and with poor LVEF (EF < 35%), poor preoperative pulmonary function (FEV1/FVC < 60% or FEV1 < 1.5 L), active congestive heart failure, preoperative renal insufficiency (serum creatinine > 180 µmol/L) or body mass index > 35 | |
| Interventions | Early extubation (within 1 hour after surgery) in 17 participants Usual care (extubation done 3 hours after surgery) in 18 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of tracheal reintubation Risk of major bleeding Time to extubation | |
| Notes | Participants were extubated in the Recovery Room rather than in the ICU. Maximum time to meet extubation criteria was 90 minutes in the early extubation group and 6 hours in the conventional extubation group. Both groups had the same sufentanil‐based general anaesthesia. No power calculation was done. No details about funding source were given. Details of any declarations of conflict of interest among study authors were not provided.or any declarations of conflict of interest among authors | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | Chest radiologist and pulmonary technologist were blinded to the study group. |
| Incomplete outcome data (attrition bias) | Low risk | Three participants withdraw from the study for not meeting extubation criteria. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected were reported. |
| Other bias | Low risk | "Preoperative and intraoperative variables were comparable between two groups" |
| Methods | Parallel‐group randomized controlled trial, conducted in France. Study conducted from June 2001 to October 2002 | |
| Participants | 51 patients scheduled for coronary artery bypass (CABG) and/or aortic valve replacement surgery were enrolled. Excluded were patients undergoing repeat cardiac surgery, likely to have a difficult intubation or with insulin‐dependent diabetes, severe pulmonary hypertension, acquired or congenital coagulation or chronic conditions likely to require more than 48 hours in the ICU after surgery | |
| Interventions | Early extubation (target controlled infusion of propofol, sufentanil (mean dose 62 μg), monitoring of anaesthetic depth by BIS index spectral analysis of electroencephalogram and extubation immediately after surgery) in 20 participants Usual care (anaesthesia technique chosen by attending anaesthetist with higher sufentanil dose (mean dose 120 μg), extubated between 4 and 6 hours after surgery) in 20 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of tracheal reintubation Time to extubation Length of stay in the ICU Total cost of drugs and disposable medical devices | |
| Notes | French paper. No power calculation was done. No details were given about funding source. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | Reasons for 11 withdrawals given |
| Selective reporting (reporting bias) | Low risk | Outcomes collected and reported |
| Other bias | Low risk | Preoperative characteristics were similar between the 2 groups. |
| Methods | Parallel‐group randomized controlled trial, conducted in Sweden. Study dates not reported | |
| Participants | 60 elective coronary artery bypass or aortic valve replacement surgery patients | |
| Interventions | Early extubation (about 2 hours after surgery) in 30 participants Usual care (about 6 hours after surgery) in 30 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of mortality at 30 days after surgery Time to extubation Length of stay in hospital | |
| Notes | Both groups received the same propofol and remifentanil‐based anaesthesia. The study focused on postoperative pain scores. No power calculation was done. No details about funding source were given. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Low risk | Sealed envelopes |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | "Three patients in late extubation group excluded because of incomplete data protocol" |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Participant demographics, anaesthesia drugs used and type of surgery were similar between the 2 groups. |
| Methods | Parallel‐group single‐blinded randomized controlled trial, conducted in Germany. Study conducted from May 2008 to July 2009 | |
| Participants | 200 patients undergoing elective cardiac surgery (coronary artery bypass graft with or without valve surgery) who were haemodynamically stable The attending anaesthesiologist and the cardiac surgeon in consensus excluded those who were in cardiogenic shock, were dialysis dependent or had an additive EuroSCORE > 10 before surgery, as well as those with impaired left ventricular function (ejection fraction < 35%), cardiac assist devices preoperative or postoperative and cardiopulmonary instability (high inotropic support, lactate > 5 mmol/L, Horowitz index < 200) after surgery | |
| Interventions | Early extubation group (100 participants): postoperative care in post‐anaesthetic care unit (PACU) with high physician‐to‐patient ratio of 1:3. Weaning protocol was driven by physician with good compliance. Participants were extubated as soon as criteria were met. Usual care group (100 patients): postoperative care in ICU with low physician‐to‐patient ratio of 1:12. Weaning protocol was mainly driven by nurse. Compliance with protocol was dependent on actual workload in the ICU. Participant was extubated when criteria were met, and when the overall situation in the ICU was favourable, as estimated by the physician. Extubation criteria (same for both groups): conscious and obeys commands, stable spontaneous ventilation with pressure support of 10 to 12 cm H2O, positive end‐expiratory pressure (PEEP) 5 cm H2O, fraction of inspired oxygen (FiO2) ≤ 0.4, haemodynamically stable, not bleeding (drain output ≤ 100 mL/h) and no significant electrocardiographic abnormalities | |
| Outcomes | Time to extubation Length of stay in the ICU or in the PACU according to treatment allocation Length of stay in hospital Risk of tracheal reintubation Risk of stroke (new transient or permanent motor or sensory deficit of central origin or unexplained coma) Risk of hospital mortality | |
| Notes | Power calculation done. Funding from Leipzig Heart Center, University of Leipzig. Study authors declare no conflict of interest in the study. Not included in reintubation subgroup analysis, as extubation occurred in different locations (PACU or ICU) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Low risk | Sealed envelopes picked out of a box |
| Blinding (performance bias and detection bias) | Low risk | Medical and nursing staff in ICU and PACU had been informed about the design and conduct of the study but were not informed as to which patients were enrolled in the study. Data collection and analysis were performed by an independent person who was not part of the anaesthetic, surgical or ICU team, and who was not blinded to treatment allocation. |
| Incomplete outcome data (attrition bias) | Low risk | 423 patients consented to participated in the study at the premedication visit, 223 were excluded at the end of surgery because they met exclusion criteria at the end of surgery, or because PACU and ICU beds were not simultaneously available. |
| Selective reporting (reporting bias) | Low risk | Reported all outcomes collected |
| Other bias | Low risk | Groups were comparable at baseline except for duration of surgery and anaesthesia time. |
| Methods | Parallel‐group randomized controlled trial, conducted in the United States. Study dates not reported | |
| Participants | 38 elective coronary artery bypass graft patients with normal and slightly impaired left ventricular function | |
| Interventions | Early extubation within 8 hours of surgery in 18 participants Usual care: extubation applied in the morning of the first day after surgery in 20 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Risk of tracheal reintubation Risk of postoperative myocardial infarction (increase in myocardial enzyme values, positive technetium pyrophosphate scan and meeting predefined electrocardiographic criteria) Risk of major bleeding (necessitating surgical control) Risk of stroke Time to extubation Length of stay in the ICU | |
| Notes | Inhalation‐based anaesthesia was the same in both groups, but weaning criteria were applied earlier in the early extubation group. No power calculation was done. Study was supported, in part, by UPHS Grant (grant number: GMS‐15571‐10,11). Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | Assessors for diagnosis of myocardial infarction were blinded to group allocation. |
| Incomplete outcome data (attrition bias) | High risk | Two participants failed to meet the early extubation criteria and were excluded from data analysis on time to extubation. |
| Selective reporting (reporting bias) | Low risk | Reported all outcomes collected |
| Other bias | Low risk | Baseline characteristics were similar for age, weight, gender, preoperative ventricular function and preoperative pulmonary function. |
| Methods | Parallel‐group blinded randomized controlled trial, conducted in Spain. Study conducted from February 1994 to March 1995 | |
| Participants | 404 elective, urgent and emergency coronary artery bypass graft (CABG) patients, CABG + valve, valve surgery | |
| Interventions | Early extubation (first trial for spontaneous ventilation 6 hours after ICU admission) in 201 participants Usual care (first trial for spontaneous ventilation at 08:00 h on the day after surgery) in 203 participants Doctor decided when to extubate. | |
| Outcomes | Risk of mortality in the ICU Risk of mortality at 30 days after hospital discharge Risk of postoperative myocardial infarction (new Q wave in ECG together with increases in CPK‐MB enzyme in sequential determinations with a typical pattern) Risk of wound infection (purulent discharge or positive culture of exudate from sternal wound) Risk of acute renal failure (plasma creatinine increase ≥ 2 mg/dL above preoperative level) Risk of stroke (new and persistent neurological deficit or central nervous system damage documented on CT scan or nuclear MRI) Risk of sepsis (pathogen isolated in blood culture not related to local infection, with fever > 38.0°C or hypotension) Risk of tracheal reintubation Time to extubation Length of stay in the ICU | |
| Notes | Weaning protocol was the same in both groups, but timing was different, as described in the paper. Same high‐dose opioid‐based general anaesthesia was given in both groups. No power calculation was done. Study was supported by Fondo de Investigacion Sanitaria de la Seguridad Social (grant number: 94/0178). Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "A computer‐generated allocation schedule was applied to randomly assign in blocks of 20 to early extubation or conventional extubation group" |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | "Chest radiograph and ECGs were examined by two independent observers unaware of the patient group and blinded of each other's interpretation" |
| Incomplete outcome data (attrition bias) | Low risk | No participants were unavailable for follow‐up. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Participants' characteristics, preoperative and operative characteristics, were similar between groups. Of the 35 perioperative characteristics examined, only the prevalence of obesity and hypertension differed between groups. |
| Methods | Parallel‐group randomized controlled trial, conducted in Japan. Study dates not reported | |
| Participants | 40 elective coronary artery bypass graft, mitral valve or aortic valve replacement surgery patients | |
| Interventions | Low‐dose opioid (mean fentanyl 7.6 ± 1.6 μg/kg and isoflurane/nitrous oxide) in 20 participants High‐dose opioid (mean fentanyl 99 ± 5.8 μg/kg and nitrous oxide) in 20 participants Details of who decided when to extubate were not given. | |
| Outcomes | Time to extubation Length of stay in the ICU Length of stay in hospital | |
| Notes | Japanese article. No power calculation was done. No details about funding source were given. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawal from the study |
| Selective reporting (reporting bias) | High risk | Mortality and postoperative complications not reported |
| Other bias | Low risk | Preoperative and intraoperative characteristics were similar in the 2 groups: age, sex, height, weight, body surface area, ejection fraction, duration of surgery, duration of anaesthesia, CPB duration and aortic clamping time. |
| Methods | Parallel‐group randomized controlled trial, conducted in Egypt. Study conducted from February 2011 to October 2013 | |
| Participants | 52 elective open heart surgery adult (> 18 years) patients Excluded were patients undergoing emergency/redo operations, patients already intubated preoperatively and patients with preoperative uncontrolled diabetes (HbA1C > 5.9 mg/dL), cardiogenic shock, poor left ventricular function (ejection fraction < 45%), severe pulmonary hypertension (pulmonary artery systolic pressure > 55 mmHg) or severe renal impairment (creatinine clearance < 50 mL/min), or on regular dialysis, and patients deliberately kept intubated for haemodynamic instability and/or concerns of postoperative bleeding | |
| Interventions | Early extubation group (26 participants): Inhalational anaesthetic concentration was reduced gradually to 0.4 expired minimum alveolar concentration at completion of surgery, and residual muscle relaxation was antagonized with neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg) if extubation criteria were met in the operating theatre. Participants were transferred to ICU after extubation Extubation criteria for early extubation: SpO2 > 95% with FiO2 < 0.6, ETCO2 < 50 mmHg, spontaneous respiratory rate < 24 min and train of four (TOF) > 90% Usual care group (26 participants): Participants were transferred to the ICU intubated and sedated with propofol infusion (50 to 70 μg/kg/min) and morphine (10 to 20 μg/kg/h) while mechanical ventilation was continued in 26 participants. Sedation was discontinued in the ICU according to local ICU protocol. Extubation criteria for usual care group: awake and able to respond comprehensively to simple verbal commands, haemodynamically stable, normal ventilatory mechanics, acid‐base status, PaO2 and PaCO2 at an inspired FiO2 of 0.4 | |
| Outcomes | Time to extubation Length of stay in the ICU Risk of tracheal reintubation Risk of myocardial ischaemia (ST‐segment elevation or depression on ECG, creatinine kinase, creatinine kinase‐myocardial band and troponin I) Risk of bleeding (excessive mediastinal bleeding defined as 400 mL in the first hour, 200 mL/h for the first 6 hours or total drainage of 1000 mL at any time) Risk of acute renal failure (diminished urine output < 0.5 mL/kg/h and/or rising creatinine level) | |
| Notes | Power calculation was done. No details about funding source were given. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization was performed by computer‐generated sequence. |
| Allocation concealment (selection bias) | Low risk | Opaque sealed envelopes were used for concealment. |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No withdrawals from the study |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | High risk | More participants in the conventional group had DM, and they had longer operating time, bypass time and cross‐clamping time and consumed more morphine during the operation compared with the early extubation group |
| Methods | Parallel‐group randomized controlled trial, conducted in England from June 1991 to September 1992 | |
| Participants | 77 elective cardiac (CABG and/or valve replacement) surgical patients, with low cardiac output | |
| Interventions | Low‐dose opioid (fentanyl at 15 μg/kg and propofol 4 to 8 mg/kg/h) in 37 participants High‐dose opioid (fentanyl at 60 μg/kg and midazolam 3 to 6 mg) in 33 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Time to extubation | |
| Notes | Results reported without variability measures (standard deviation, standard errors), thus could not be included in meta‐analyses, except for total hospital costs. No power calculation was done. Funding source was Zeneca Pharma. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | Reasons for withdrawal of 7 participants from the study are given in the text (3 patients in early extubation group and 4 in the conventional group did not follow protocol). |
| Selective reporting (reporting bias) | High risk | Postoperative complications and mortality not reported. Variability measures not reported for most outcomes |
| Other bias | Low risk | All characteristics were comparable for age, weight, type of operation and ventricular function and blood gases, except gender distribution. |
| Methods | Parallel‐group randomized controlled trial, conducted in Australia. Study dates not reported | |
| Participants | 100 elective coronary artery bypass graft patients, with good and moderate left ventricular function. Excluded were patients with concurrent valve disease, poor myocardial function, associated systemic illness, contraindications to early extubation (e.g. respiratory disease) or communication problems (language or psychiatric) | |
| Interventions | Low‐dose opioid (fentanyl 15 μg/kg with propofol infusion) in 38 participants High‐dose opioid (fentanyl 50 μg/kg with propofol or additional fentanyl infusion) in 46 participants Decision to extubate when criteria were met was made in consultation with the attending doctor. | |
| Outcomes | Risk of mortality at hospital discharge Time to extubation Length of hospital stay | |
| Notes | Weaning criteria were reported and applied to both groups. One participant from each group died, and all were withdrawn from the study. One participant in the early extubation group died 2 months after surgery. No power calculation was done. Study was supported, in part, by a research grant provided by the Australian Society of Anaesthetists and Abbott Australasia, and by a grant‐in‐aid provided by ICI Pharmaceuticals. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization was performed by computer‐generated random numbers (in blocks of 4) to conventional extubation group or early extubation group. |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | High risk | "No attempt was made to blind ICU staff to treatment group, as a pilot study had previously shown that those patients in the early extubation group became readily apparent" |
| Incomplete outcome data (attrition bias) | Low risk | Clear description of withdrawals from study before and after anaesthesia was given |
| Selective reporting (reporting bias) | High risk | ICU length of stay stated as collected outcome, but no results given in text |
| Other bias | Low risk | Demographic data similar for both groups |
| Methods | Parallel‐group double‐blinded randomized controlled trial, conducted at 3 hospitals in Australia. Study conducted from June 2001 to December 2003 | |
| Participants | 350 elective first‐time coronary artery bypass graft patients, 55 years of ag or older, with no previous neurological deficit and able to undergo neuropsychological testing | |
| Interventions | Low‐dose opioid (mean fentanyl 9.9 ± 1.1 μg/kg) in 168 participants High‐dose opioid (fentanyl 50.0 ± 2.4 μg/kg) in 158 participants Details of who decided when to extubate were not given. | |
| Outcomes | Risk of hospital mortality Risk of mortality at 3 months and 1 year Time to extubation Length of time in the ICU Length of stay in hospital | |
| Notes | For purposes of analysis, hospital mortality and 1‐year mortality data were used. Power calculation was done. Funding sources were the National Health and Medical Research Council, Canberra, Australian Capital Territory, Australia (Project Grant No. 140510), and a National Health and Medical Research Council Practitioner Fellowship awarded to the seventh review author. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Random number tables and stratification by institution (3 sites) |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | Neurological test administered by a trained interviewer, who was blinded to participants' allocation |
| Incomplete outcome data (attrition bias) | Low risk | Participants who withdrew were described and the reasons given. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Demographic data were similar for the 2 groups. |
| Methods | Parallel‐group randomized controlled trial, conducted in Italy. Study conducted from February 1999 to November 1999 | |
| Participants | 49 elective coronary artery bypass graft, aortic or mitral valve surgery patients | |
| Interventions | Early extubation (weaning protocol with aim of extubation within 9 hours after surgery) in 24 participants Usual care (weaning according to physicians' subjective clinical judgement) in 25 participants Physicians decided when to extubate. | |
| Outcomes | Risk of tracheal reintubation Risk of stroke (e.g. aphasia, right side paralysis) Risk of major bleeding Risk of acute renal failure Time to extubation Length of stay in the ICU | |
| Notes | Weaning protocol was the same in both groups, but timing was different, as described in the paper. No power calculation was done. No details about the funding source were given. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | No details given |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Unclear risk | No details given |
| Incomplete outcome data (attrition bias) | Low risk | No participants withdrew from the study. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Preoperative risk score, participants' characteristics, surgical time, illness severity score (APACHE II and III) and preoperative respiratory parameters were comparable between groups. |
| Methods | Parallel 4‐arm randomized controlled trial, conducted in the United States. Study conducted from September 1985 to July 1987 | |
| Participants | 1012 patients 21 to 75 years of age, scheduled for elective CABG by 4 participating surgeons. Excluded were patients with previous cardiac operation, emergency operation, operations performed in addition to CABG, severe systemic non‐cardiac disease other than diabetes and hypertension, history of allergy to any drugs that might be administered and preoperative EEG that precluded diagnosis of ischaemia, such as LBBB. | |
| Interventions | Low‐dose opioid (fentanyl 10 μg/kg and enflurane, halothane or Isoflurane) in 758 participants High‐dose opioid (mean sufentanil 28 ± 4 μg/kg) in 254 participants Details of weaning protocol and who decided when to extubate were not given. | |
| Outcomes | Risk of hospital mortality Risk of postoperative myocardial infarction (new Q waves ≥ 0.04 seconds, or extended old Q waves, or LBBB presence, and CPK‐MB > 80U) Time to extubation | |
| Notes | Enflurane, halothane and isoflurane groups were combined as a single low‐dose opioid group for meta‐analyses. Power calculation was done. Details of any declarations of conflict of interest among study authors were not provided. Study was supported in part by Janssen Pharmaceutica. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "Primary drug assignment was randomized for each four surgeons from four different tables of random number" |
| Allocation concealment (selection bias) | Unclear risk | No details given |
| Blinding (performance bias and detection bias) | Low risk | "All data were collected by trained observers who did not participate in patients care" "The ECG traces were reviewed by one investigator who was unaware of the patient, anaesthetic, operative event, or intervention" |
| Incomplete outcome data (attrition bias) | Low risk | "Data of all patients were pooled and subjected to stepwise discriminant analysis of all factors listed in table 1" |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported. "The five patients who died of PMI were included in the group considered to have PMI; the 12 others were included in the group without PMI" |
| Other bias | Low risk | "Of 34 characteristics compared, the only significant differences between primary anaesthesia groups were in the incidence of history of chronic hypertension and mean preoperative systolic blood pressure" |
| Methods | Parallel‐group single‐blinded randomized clinical trial, conducted in Netherlands. Study conducted from February 2001 to March 2003 | |
| Participants | 600 patients admitted to the University Hospital for CABG surgery in the period from March 2001 until February 2003 with low risk stratified by Parsonnet score | |
| Interventions | Early extubation (short‐stay ICU treatment and extubation < 8 hours) in 300 participants Usual care (stay overnight in the ICU as usual practice and extubated) in 300 participants ICU physicians decided when to extubate. | |
| Outcomes | Risk of death at 30 days Risk of myocardial infarction Risk of major bleeding Risk of wound infection Risk of stroke Risk of acute renal failure Time to extubation Length of stay in the ICU Length of stay in hospital Total hospital cost (nutrition, laundry, accommodation, cleaning, overheads, equipment, staff, material and medication) Change in quality of life (ED‐5D) at 1 month and 1 year from baseline | |
| Notes | One participant in the early extubation group died during surgery and was excluded from study author's main analysis. During surgery, participants were anaesthetized with "total intravenous infusions of propofol and a short acting opioid." Quality of life data were taken from 2010 paper (n = 408). Power calculation was done. No details about funding source were given. Details of any declarations of conflict of interest among study authors were not provided. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "A random list of permuted blocks (with a length of 10) was generated for either control (n=300) or SSIC (n=300) by a computer" |
| Allocation concealment (selection bias) | Low risk | The generated sequence was entered "sequentially into numbered, opaque, sealed envelopes sealed with tape" |
| Blinding (performance bias and detection bias) | Low risk | Participants and the surgical team were blinded for group assignments. The physician was not blinded but was not aware that ICU readmission was one of the 2 primary endpoints of the study. |
| Incomplete outcome data (attrition bias) | Low risk | Reasons for 3 withdrawals were given. |
| Selective reporting (reporting bias) | Low risk | All death and perioperative complications collected and reported |
| Other bias | Low risk | Demographic, co‐morbidity and operative data were comparable between the 2 groups. |
| Methods | Parallel‐group unblinded randomized clinical trial, conducted in Hong Kong. Study conducted from May 2012 to March 2013 | |
| Participants | 68 patients 18 to 80 years of age, scheduled for elective cardiac valvular surgery (isolated valve surgery and valve surgery combined with another cardiac surgical procedure). Excluded were patients with acute or chronic obstructive pulmonary disease, serum creatinine concentration > 200 μmol/L, serum aspartate transaminase concentration > 80 U/L, left ventricular ejection fraction < 30% and history of seizures or stroke before surgery; as well as patients with chest tube drainage > 500 mL/h, reoperation, myocardial infarction, need for high‐dose inotropes or vasopressors or intra‐aortic balloon pump and with refractory hypoxaemia with arterial oxygen tension‐to‐fractional inspired oxygen concentration ratio < 150 mmHg after surgery. | |
| Interventions | Early extubation group (25 participants): Paralysis was reversed and sedation was stopped in ICU. Weaning protocol using Adaptive Support Ventilation (ASV) with algorithm provided was used within 8 hours after ICU admission. Ventilation management was directed by duty physicians after 8 hours. Usual care group (25 participants): Paralysis was reversed and sedation was stopped in ICU. Weaning was directed by duty physicians. Extubated criteria (same in both groups): responsive and cooperative; Fio2 < 40%; PaO2/FiO2 > 150 mmHg; positive end‐expiratory pressure (PEEP) ≤ 5 cm H2O; haemodynamically stable; urine output exceeds 0.5 mL kg−1 h−1; last hour chest tube drainage < 100 mL; no uncontrolled arrhythmia; and rectal temperature above 36.0°C | |
| Outcomes | Time to extubation Length of stay in the ICU Length of stay in hospital Risk of bleeding (unpublished data) Risk of stroke Risk of sepsis (unpublished data) Risk of acute renal failure (defined as new haemofiltration and dialysis) Risk of tracheal reintubation Risk of hospital mortality | |
| Notes | The 2 ventilators were borrowed from Hamilton Medical GA, Rhäzuns, Switzerland. Power calculation was done. Funding source was the department. Details of any declarations of conflict of interest among study authors were not provided. Intention‐to‐treat analysis data reported in the paper were extracted for meta‐analyses. Study authors had access to raw RCT data. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Randomization was performed by computer‐generated sequence. |
| Allocation concealment (selection bias) | Low risk | Opaque sealed envelopes containing treatment allocation were opened after the participant's arrival to the ICU. |
| Blinding (performance bias and detection bias) | High risk | ICU staff and outcome assessor not blinded to treatment allocation |
| Incomplete outcome data (attrition bias) | Low risk | Thirty‐four participants were randomized to each group, but 4 participants in the ASV group and 3 in the control group were excluded postoperatively with reasons given; protocol violations occurred in 5 participants in the ASV group and in 3 participants in the control group. |
| Selective reporting (reporting bias) | Low risk | All outcomes collected and reported |
| Other bias | Low risk | Demographic, preoperative and intraoperative parameters were comparable in the 2 groups, except for increased prevalence of preoperative atrial fibrillation in the usual care group and increased total dose of intraoperative propofol in the early extubation group. |
APACHE: Acute Physiology And Chronic Health Evaluation; ASV: Adaptive Support Ventilation; BIS: bispectral index; BMI: body mass index; CABG: coronary artery bypass grafting; CK: creatine kinase; CK‐MB: creatine kinase MB isoenzyme; cm: centimeter; CPB: cardiopulmonary bypass; CPK: creatine phosphokinase; CPK‐MB: creatine phosphokinase MB isoenzyme; CT scan: computed tomography scan; DM: diabetes mellitus; ECG: electrocardiography; ED‐5D: health questionnaire providing a simple descriptive profile and a single index value for health status; ETCO2: end‐tidal carbon dioxide; EuroSCORE: European System for Cardiac Operative Risk Evaluation; FEV1: forced expiratory volume in one second; FiO2: fractional inspiratory oxygen; FVC: forced vital capacity; h: hour; HbA1C: glycated haemoglobin; ICU: intensive care unit; IU/L: international unit per litre; IV: intravenous; km: kilometre; LBBB: left bundle branch block; LV: left ventricle; LVEF: left ventricular ejection fraction; mg: milligram; mg/dL: milligram per decilitre; mL/h: millilitre per hour; MRI: magnetic resonance imaging; n: number of participants; NYHA: New York Heart Association; OT: operating theatre; PACU: post‐anaethetic care unit; PaO2: arterial partial pressure of oxygen; PEEP: positive end‐expiratory pressure; PMI: postoperative myocardial infarction; PO2: partial pressure of oxygen; QRS: QRS complex in electrocardiography; RCT: randomized controlled trial; SpO2: arterial oxygen saturation; SSIC: short stay intensive care; ST: ST segment in electrocardiography; TOF: train of four; μg/kg: microgram per kilogram; μg/kg/min: microgram per kilogram per minute; μmol/L: micromole per litre; U: unit; U/L: unit per litre; UPHS: University of Pennsylvania Health System; USD: United States dollar.
Characteristics of excluded studies [ordered by study ID]
Ir a:
| Study | Reason for exclusion |
| Intervention not relevant. Group A included participants who were operated on with the minimal extracorporeal circulation circuit, whereas those in Group B underwent surgery on conventional cardiopulmonary bypass. | |
| Not a randomized controlled trial | |
| Turkish study. Not a randomized controlled trial | |
| Comparison of remifentanil group (induction with remifentanil 1 μg/kg/min/isoflurane/propofol; remifentanil maintenance dose of 1 μg/kg) vs fentanyl group (induction with fentanyl 10 μg/kg bolus, fentanyl maintenance dose of 2 μg/kg). Both groups had isoflurane or enflurane and propofol maintenance. The type of anaesthesia given in both groups was considered fast‐track cardiac anaesthesia by study authors. | |
| RCT comparing sevoflurane vs isoflurane as the primary anaesthetic agent. Both groups were given a total of fentanyl 5 μg/kg during surgery. | |
| All groups were given low‐dose sufentanil. | |
| Investigators used a historical control instead of a randomized controlled trial study design. | |
| All participants recruited received low‐dose opioid‐based general anaesthesia (Group 1: median fentanyl dose 9.0 μg/kg; Group 2: median sufentanil dose 1.7 μg/kg; Group 3: median remifentanil 88 μg/kg and fentanyl 2.9 μg/kg). All participants aimed to be extubated by 6:30 am on the first postoperative day. No high‐dose opioid comparison group was included. All groups had the same weaning protocol. | |
| Study did not recruit cardiac patients undergoing surgery. | |
| Five groups had differing predicted sufentanil effect site concentrations (0.5 ng/mL, 0.75 ng/mL, 1 ng/mL, 1.25 ng/mL and 1.5 ng/mL) with target propofol concentration of 1.5 μg/mL. No details about mean weight were given for each group. Corresponding cumulative mean (SD) sufentanil doses (μg/kg) were 165 (20), 229 (38), 300 (49), 355 (56) and 440 (107). All groups had the same weaning protocol with the aim of extubation within 8 hours of surgery. No high‐dose opioid or time‐directed extubation protocol comparative groups were included to meet systematic review inclusion criteria. | |
| Comparison of sufentanil (mean 3.0 ± 0.6 μg/kg) vs remifentanil (mean 96.6 ± 39.1 μg/kg with clonidine); both groups had propofol infusion. Remifentanil used was high dose but has a short plasma half‐life. No details of weaning protocol provided. The type of anaesthesia given in both groups was considered fast‐track cardiac anaesthesia by study authors. | |
| Article in Polish. Not able to get full text | |
| Comparison of Group A (propofol‐sufentanil) and Group B (enflurane‐sufentanil anaesthesia), but this anaesthesia regimen was not given for fast‐tracking purposes. Mean time to extubation in Group A was 26.9 ± 15.7 hours and for Group B was 29.5 ± 27.0 hours, respectively | |
| Comparison of Group A (combined thoracic epidural analgesia and general anaesthesia followed by patient‐controlled thoracic epidural analgesia) and Group B (general anaesthesia followed by patient‐controlled analgesia with intravenous morphine). Does not fit systematic review inclusion criteria | |
| Comparison of different doses of sufentanil during induction. Study ended 2 minutes after endotracheal intubation. | |
| Comparison of 4 groups (alfentanil, high‐dose remifentanil, low‐dose remifentanil, thoracic epidural group); all fast‐track anaesthetic techniques. All groups had the same weaning protocol. No relevant outcomes were reported in the paper. | |
| Randomized to 1 of 3 remifentanil groups: Group 1 (1 μg/kg/min), Group 2 (2 μg/kg/min) and Group 3 (3 μg/kg/min). Total remifentanil doses administered (μg/kg) for Group 1, Group 2 and Group 3 were 716 ± 231, 879 ± 204 and 1174 ± 301, respectively. All groups aimed to be extubated within 6 hours after ICU admission. | |
| Does not fit inclusion criteria for systematic review. Intrathecal low‐dose morphine compared with intrathecal normal saline | |
| Not a randomized controlled trial | |
| Comparison of remifentanil‐based anaesthesia (0.5 μg/kg/min) and fentanyl 2.5 μg/kg/h supplemented with additional standard bolus doses 5 μg/kg during induction and before skin incision. Does not fit inclusion criteria for systematic review. No relevant outcomes | |
| Not a randomized controlled trial. The trial was excluded in published reviews (Hawkes 2003; Zhu 2012). | |
| Retracted article | |
| Comparison of Group 1: remifentanil and spinal analgesia (low‐dose morphine and clonidine) and Group 2: sufentanil without spinal analgesia. Does not fit systematic review inclusion criteria | |
| Comparison of Group 1: remifentanil and spinal analgesia (low‐dose morphine and clonidine) and Group 2: sufentanil without spinal analgesia. Does not fit systematic review inclusion criteria | |
| Comparison of isoflurane (0.4 to 0.8 vol%) together with either remifentanil group (1 μg/kg/min) or sulfentanil group (1 μg/kg for induction, 0.5 μg/kg for skin incision, then 0.02 μg/kg/min). Both groups were given what were considered fast‐track cardiac anaesthesia regimens with expected extubation within 8 hours after surgery. No late extubation group for comparison. Both groups had the same weaning protocol. | |
| Comparison of parasternal block and local anaesthetic infiltration of the sternotomy wound and mediastinal tube sites with levobupivacaine vs placebo. Both groups were given a desflurane‐based, low‐dose opioid anaesthetic. Does not fit systematic review inclusion criteria | |
| Multi‐centre RCT comparing high‐dose remifentanil by continuous infusion vs an intermittent bolus fentanyl regimen, both given in combination with propofol. No details about average or cumulative opioid doses used during surgery to classify 'high‐' versus 'low‐'dose opioid‐based cardiac anaesthesia | |
| Comparison of morphine 40 mg and fentanyl 600 μg as part of a standardized opioid‐isoflurane anaesthetic. Both groups considered as low‐dose opioid. In both groups, decisions on weaning, tracheal extubation, ICU and hospital discharge were standardized and were made by the surgical team, who were blinded to treatment allocation. Both groups were extubated after 8 hours following surgery (i.e. both groups were not fast‐tracked). | |
| Not a randomized controlled trial | |
| Postoperative sedation and analgesia regimen comparisons. All groups had the same standardized weaning protocol. | |
| Bispectral index monitoring was the focus of this randomization. | |
| Comparison of 3 high‐dose opioid‐based anaesthesia groups: (1) isoflurane and mean sufentanil 5 μg/kg, (2) enflurane and mean sufentanil 5 μg/kg, (3) no volatile agent and mean sufentanil 10.8 μg/kg. Study authors measured the risk of perioperative myocardial infarction. Data for postoperative myocardial infarction were not available. Fast‐track extubation was not the intention of the study. | |
| Not a randomized controlled trial | |
| Comparison of high thoracic epidural analgesia and intravenous morphine analgesia | |
| Comparison of Group 1 (10 μg/kg morphine and 25 μg fentanyl intrathecally preoperatively) vs Group 2 (no intrathecal opioid but 25 to 50 μg/kg fentanyl given intraoperatively) | |
| Comparison of adaptive support ventilation vs synchronized intermittent mandatory ventilation. Both groups had formalized weaning protocols. | |
| Elective closed mitral valvotomy surgery. Does not fit participants' inclusion criteria | |
| Similar fentanyl total dose used between propofol and isoflurane groups (mean 1230 ± 170 μg and mean 1252 ± 218 μg, respectively). Early extubation was not the focus of the study. | |
| Article in Turkish. No full text available | |
| Article in Turkish. No full text available |
ICU: intensive care unit; ng/mL: nanogram per millilitre; RCT: randomized controlled trial ; SD: standard deviation; μg/kg: microgram per kilogram; μg/kg/min: microgram per kilogram per minute; vol: volume.
Data and analyses
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality Show forest plot | 8 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| Analysis 1.1  Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 1 Mortality. | ||||
| 1.1 Death in hospital after surgery | 7 | 1896 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.58 [0.24, 1.39] |
| 1.2 Death at 1 year after surgery | 2 | 446 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.55 [0.17, 1.82] |
| 1.3 Death at any time after surgery | 8 | 1994 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.53 [0.25, 1.12] |
| 2 Postoperative complications Show forest plot | 10 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| Analysis 1.2  Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 2 Postoperative complications. | ||||
| 2.1 Postoperative myocardial infarction | 8 | 1683 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.48, 1.99] |
| 2.2 Stroke | 5 | 562 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.36, 3.78] |
| 2.3 Acute renal failure | 4 | 492 | Risk Ratio (IV, Random, 95% CI) | 1.19 [0.33, 4.33] |
| 2.4 Major bleeding | 4 | 469 | Risk Ratio (IV, Random, 95% CI) | 0.48 [0.16, 1.44] |
| 2.5 Reintubation | 5 | 594 | Risk Ratio (IV, Random, 95% CI) | 1.77 [0.38, 8.27] |
| 3 Service outcomes Show forest plot | 14 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| Analysis 1.3  Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 3 Service outcomes. | ||||
| 3.1 Time to extubation (hours) | 14 | 2486 | Mean Difference (IV, Random, 95% CI) | ‐7.40 [‐10.51, ‐4.29] |
| 3.2 Length of intensive care unit stay (hours) | 12 | 1394 | Mean Difference (IV, Random, 95% CI) | ‐3.70 [‐6.98, ‐0.41] |
| 3.3 Length of hospital stay (days) | 8 | 913 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐1.04, 0.43] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality Show forest plot | 10 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| Analysis 2.1  Comparison 2 Time‐directed extubation protocol, Outcome 1 Mortality. | ||||
| 1.1 Death in the intensive care unit | 2 | 370 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.87 [0.19, 3.88] |
| 1.2 Death in hospital after surgery | 5 | 582 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.23 [0.05, 1.04] |
| 1.3 Death at 1 month after surgery | 4 | 1122 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.13 [0.59, 2.19] |
| 1.4 Death at any time after surgery | 10 | 1802 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.80 [0.45, 1.45] |
| 2 Postoperative complications Show forest plot | 15 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| Analysis 2.2  Comparison 2 Time‐directed extubation protocol, Outcome 2 Postoperative complications. | ||||
| 2.1 Postoperative myocardial infarction | 8 | 1378 | Risk Ratio (IV, Random, 95% CI) | 0.59 [0.27, 1.31] |
| 2.2 Stroke | 11 | 1646 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.33, 2.16] |
| 2.3 Acute renal failure | 9 | 1541 | Risk Ratio (IV, Random, 95% CI) | 1.11 [0.42, 2.91] |
| 2.4 Major bleeding | 10 | 1244 | Risk Ratio (IV, Random, 95% CI) | 0.92 [0.53, 1.61] |
| 2.5 Major sepsis | 3 | 477 | Risk Ratio (IV, Random, 95% CI) | 2.40 [0.31, 18.25] |
| 2.6 Wound infection | 2 | 868 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.25, 1.83] |
| 2.7 Reintubation | 12 | 1261 | Risk Ratio (IV, Random, 95% CI) | 1.34 [0.74, 2.41] |
| 3 Service outcomes Show forest plot | 16 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| Analysis 2.3  Comparison 2 Time‐directed extubation protocol, Outcome 3 Service outcomes. | ||||
| 3.1 Time to extubation (hours) | 16 | 2024 | Mean Difference (IV, Random, 95% CI) | ‐6.25 [‐8.84, ‐3.67] |
| 3.2 Length of intensive care unit stay (hours) | 13 | 1888 | Mean Difference (IV, Random, 95% CI) | ‐7.16 [‐10.45, ‐3.88] |
| 3.3 Length of hospital stay (days) | 8 | 1334 | Mean Difference (IV, Random, 95% CI) | ‐0.44 [‐1.04, 0.16] |
| 4 Subgroup analysis Show forest plot | 11 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| Analysis 2.4  Comparison 2 Time‐directed extubation protocol, Outcome 4 Subgroup analysis. | ||||
| 4.1 Reintubation after extubation in ICU | 8 | 934 | Risk Ratio (IV, Random, 95% CI) | 1.99 [0.93, 4.23] |
| 4.2 Reintubation after extubation outside ICU | 3 | 127 | Risk Ratio (IV, Random, 95% CI) | 3.82 [0.44, 33.24] |
Study flow diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Forest plot of comparison: 2 Time‐directed extubation protocols, outcome: 2.4 Subgroup analysis.
Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 1 Mortality.
Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 2 Postoperative complications.
Comparison 1 Dose of opioid‐based cardiac anaesthesia, Outcome 3 Service outcomes.
Comparison 2 Time‐directed extubation protocol, Outcome 1 Mortality.
Comparison 2 Time‐directed extubation protocol, Outcome 2 Postoperative complications.
Comparison 2 Time‐directed extubation protocol, Outcome 3 Service outcomes.
Comparison 2 Time‐directed extubation protocol, Outcome 4 Subgroup analysis.
| Low‐dose opioid‐based general anaesthesia compared with high‐dose opioid‐based general anaesthesia for adults undergoing cardiac surgery | ||||||
| Patient or population: adult cardiac surgical patients Intervention: low‐dose opioid‐based general anaesthesia | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Risk with high‐dose opioid‐based general anaesthesia | Risk with low‐dose opioid‐based general anaesthesia | |||||
| Mortality ‐ Death at any time after surgery | Low | OR 0.53 | 1994 | ⊕⊕⊝⊝ | No death recorded in 3 trials | |
| 10 per 1000 | 5 per 1000 | |||||
| Moderate | ||||||
| 30 per 1000 | 16 per 1000 | |||||
| High | ||||||
| 110 per 1000 | 61 per 1000 | |||||
| Postoperative myocardial infarction | Study population | RR 0.98 | 1683 | ⊕⊕⊝⊝ | No postoperative myocardial infarction recorded in 2 trials | |
| 30 per 1000 | 30 per 1000 | |||||
| Postoperative stroke | Study population | RR 1.17 | 562 | ⊕⊕⊝⊝ | No stroke recorded in 1 trial | |
| 18 per 1000 | 21 per 1000 | |||||
| Postoperative tracheal reintubation | Study population | RR 1.77 | 594 | ⊕⊕⊝⊝ | No reintubation recorded in 3 trials | |
| 7 per 1000 | 12 per 1000 | |||||
| Time to extubation (hours) | Mean time to extubation (hours) was 5.2 to 35.1 | Mean time to extubation (hours) in the intervention group was 7.4 lower (10.51 lower to 4.29 lower). | ‐ | 2486 | ⊕⊕⊝⊝ | |
| Length of intensive care unit stay (hours) | Mean length of intensive care unit stay (hours) was 2.6 to 112.8. | Mean length of intensive care unit stay (hours) in the intervention group was 3.7 lower (6.98 lower to 0.41 lower). | ‐ | 1394 | ⊕⊕⊝⊝ | |
| Length of hospital stay (days) | Mean length of hospital stay (days) was 5.1 to 27.0. | Mean length of hospital stay (days) in the intervention group was 0.3 lower (1.04 lower to 0.43 higher). | ‐ | 913 | ⊕⊕⊝⊝ | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group using the EuroSCORE risk classification (Michel 2003) and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aOf the 8 trials, 2 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). bOptimal information size not met (downgrade 1 point owing to imprecision). cOf the 5 trials, 1 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). dOf the 5 trials, 2 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). eOf the 14 trials, 4 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). fUnexplained reasons for high heterogeneity. gOf the 12 trials, 3 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). hOf the 8 trials, 3 had ≥ 1 high risk of bias domain (downgrade 1 point owing to study limitations). | ||||||
| Time‐directed extubation protocol compared with usual care for adults undergoing cardiac surgery | ||||||
| Patient or population: adult cardiac surgical patients | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect | Number of participants | Quality of the evidence | Comments | |
| Risk with usual care | Risk with time‐directed extubation protocol | |||||
| Mortality ‐ Death at any time after surgery | Low | OR 0.80 | 1802 | ⊕⊕⊝⊝ | No deaths recorded in 4 trials. Low to moderate heterogeneity (I2 = 37%) may be explained by the inclusion of a trial (Reyes 1997) that had the highest rate of mortality of all trials considered. When excluded, the OR changed to 0.31 (95% CI 0.11 to 0.90, P = 0.03, I2 = 0%). | |
| 10 per 1000 | 8 per 1000 | |||||
| Moderate | ||||||
| 30 per 1000 | 24 per 1000 | |||||
| High | ||||||
| 110 per 1000 | 90 per 1000 | |||||
| Postoperative myocardial infarction | Study population | RR 0.59 | 1378 | ⊕⊕⊝⊝ | No postoperative myocardial infarction was recorded in 1 trial. | |
| 61 per 1000 | 36 per 1000 | |||||
| Postoperative stroke | Study population | RR 0.85 | 1646 | ⊕⊕⊝⊝ | No stroke was recorded in 2 trials. | |
| 12 per 1000 | 10 per 1000 | |||||
| Postoperative reintubation | Study population | RR 1.34 | 1261 | ⊕⊕⊝⊝ | No reintubation was recorded in 3 trials. | |
| 28 per 1000 | 38 per 1000 | |||||
| Time to extubation (hours) | Mean time to extubation (hours) was 3.4 to 18.9. | Mean time to extubation (hours) in the intervention group was 6.25 lower (8.84 lower to 3.67 lower). | ‐ | 2024 | ⊕⊕⊝⊝ | No variation in time to extubation in the early extubation group in 1 trial |
| Length of intensive care unit stay (hours) | Mean length of intensive care unit stay (hours) was 17.9 to 95.0. | Mean length of intensive care unit stay (hours) in the intervention group was 7.16 lower (10.45 lower to 3.88 lower). | ‐ | 1888 | ⊕⊕⊝⊝ | No variation in length of ICU stay in early extubation group in 1 trial |
| Length of hospital stay (days) | Mean length of hospital stay (days) was 5.1 to 13.0. | Mean length of hospital stay (days) in the intervention group was 0.44 lower (1.04 lower to 0.16 higher). | ‐ | 1334 | ⊕⊕⊝⊝ | |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group using the EuroSCORE risk classification (Michel 2003) and the relative effect of the intervention (and its 95% CI). | ||||||
| GRADE Working Group grades of evidence | ||||||
| aOf the 10 trials, 3 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). bOptimal information size not met (downgrade 1 point owing to imprecision). cOf the 8 trials, 3 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). dOf the 11 trials, 5 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). dOf the 12 trials, 5 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). fUnexplained reasons for high heterogeneity. gOf the 16 trials, 6 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). hOf the 13 trials, 5 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). iOf the 8 trials, 2 had 1 high risk of bias domain (downgrade 1 point owing to study limitations). | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality Show forest plot | 8 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.1 Death in hospital after surgery | 7 | 1896 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.58 [0.24, 1.39] |
| 1.2 Death at 1 year after surgery | 2 | 446 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.55 [0.17, 1.82] |
| 1.3 Death at any time after surgery | 8 | 1994 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.53 [0.25, 1.12] |
| 2 Postoperative complications Show forest plot | 10 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Postoperative myocardial infarction | 8 | 1683 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.48, 1.99] |
| 2.2 Stroke | 5 | 562 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.36, 3.78] |
| 2.3 Acute renal failure | 4 | 492 | Risk Ratio (IV, Random, 95% CI) | 1.19 [0.33, 4.33] |
| 2.4 Major bleeding | 4 | 469 | Risk Ratio (IV, Random, 95% CI) | 0.48 [0.16, 1.44] |
| 2.5 Reintubation | 5 | 594 | Risk Ratio (IV, Random, 95% CI) | 1.77 [0.38, 8.27] |
| 3 Service outcomes Show forest plot | 14 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 Time to extubation (hours) | 14 | 2486 | Mean Difference (IV, Random, 95% CI) | ‐7.40 [‐10.51, ‐4.29] |
| 3.2 Length of intensive care unit stay (hours) | 12 | 1394 | Mean Difference (IV, Random, 95% CI) | ‐3.70 [‐6.98, ‐0.41] |
| 3.3 Length of hospital stay (days) | 8 | 913 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐1.04, 0.43] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1 Mortality Show forest plot | 10 | Peto Odds Ratio (Peto, Fixed, 95% CI) | Subtotals only | |
| 1.1 Death in the intensive care unit | 2 | 370 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.87 [0.19, 3.88] |
| 1.2 Death in hospital after surgery | 5 | 582 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.23 [0.05, 1.04] |
| 1.3 Death at 1 month after surgery | 4 | 1122 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 1.13 [0.59, 2.19] |
| 1.4 Death at any time after surgery | 10 | 1802 | Peto Odds Ratio (Peto, Fixed, 95% CI) | 0.80 [0.45, 1.45] |
| 2 Postoperative complications Show forest plot | 15 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 2.1 Postoperative myocardial infarction | 8 | 1378 | Risk Ratio (IV, Random, 95% CI) | 0.59 [0.27, 1.31] |
| 2.2 Stroke | 11 | 1646 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.33, 2.16] |
| 2.3 Acute renal failure | 9 | 1541 | Risk Ratio (IV, Random, 95% CI) | 1.11 [0.42, 2.91] |
| 2.4 Major bleeding | 10 | 1244 | Risk Ratio (IV, Random, 95% CI) | 0.92 [0.53, 1.61] |
| 2.5 Major sepsis | 3 | 477 | Risk Ratio (IV, Random, 95% CI) | 2.40 [0.31, 18.25] |
| 2.6 Wound infection | 2 | 868 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.25, 1.83] |
| 2.7 Reintubation | 12 | 1261 | Risk Ratio (IV, Random, 95% CI) | 1.34 [0.74, 2.41] |
| 3 Service outcomes Show forest plot | 16 | Mean Difference (IV, Random, 95% CI) | Subtotals only | |
| 3.1 Time to extubation (hours) | 16 | 2024 | Mean Difference (IV, Random, 95% CI) | ‐6.25 [‐8.84, ‐3.67] |
| 3.2 Length of intensive care unit stay (hours) | 13 | 1888 | Mean Difference (IV, Random, 95% CI) | ‐7.16 [‐10.45, ‐3.88] |
| 3.3 Length of hospital stay (days) | 8 | 1334 | Mean Difference (IV, Random, 95% CI) | ‐0.44 [‐1.04, 0.16] |
| 4 Subgroup analysis Show forest plot | 11 | Risk Ratio (IV, Random, 95% CI) | Subtotals only | |
| 4.1 Reintubation after extubation in ICU | 8 | 934 | Risk Ratio (IV, Random, 95% CI) | 1.99 [0.93, 4.23] |
| 4.2 Reintubation after extubation outside ICU | 3 | 127 | Risk Ratio (IV, Random, 95% CI) | 3.82 [0.44, 33.24] |
