Background
Good neurological outcome after cardiac arrest is difficult to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. ...Experimental evidence suggests that therapeutic hypothermia is beneficial, and several clinical studies on this topic have been published. This review was originally published in 2009; updated versions were published in 2012 and 2016.
Objectives
We aimed to perform a systematic review and meta‐analysis to assess the influence of therapeutic hypothermia after cardiac arrest on neurological outcome, survival and adverse events.
Search methods
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10); MEDLINE (1971 to May 2015); EMBASE (1987 to May 2015); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1988 to May 2015); and BIOSIS (1989 to May 2015). We contacted experts in the field to ask for information on ongoing, unpublished or published trials on this topic.The original search was performed in January 2007.
Selection criteria
We included all randomized controlled trials (RCTs) conducted to assess the effectiveness of therapeutic hypothermia in participants after cardiac arrest, without language restrictions. We restricted studies to adult populations cooled by any cooling method, applied within six hours of cardiac arrest.
Data collection and analysis
We entered validity measures, interventions, outcomes and additional baseline variables into a database. Meta‐analysis was performed only for a subset of comparable studies with negligible heterogeneity. We assessed the quality of the evidence by using standard methodological procedures as expected by Cochrane and incorporated the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach.
Main results
We found six RCTs (1412 participants overall) conducted to evaluate the effects of therapeutic hypothermia ‐ five on neurological outcome and survival, one on only neurological outcome. The quality of the included studies was generally moderate, and risk of bias was low in three out of six studies. When we compared conventional cooling methods versus no cooling (four trials; 437 participants), we found that participants in the conventional cooling group were more likely to reach a favourable neurological outcome (risk ratio (RR) 1.94, 95% confidence interval (CI) 1.18 to 3.21). The quality of the evidence was moderate.
Across all studies that used conventional cooling methods rather than no cooling (three studies; 383 participants), we found a 30% survival benefit (RR 1.32, 95% CI 1.10 to 1.65). The quality of the evidence was moderate.
Across all studies, the incidence of pneumonia (RR 1.15, 95% CI 1.02 to 1.30; two trials; 1205 participants) and hypokalaemia (RR 1.38, 95% CI 1.03 to 1.84; two trials; 975 participants) was slightly increased among participants receiving therapeutic hypothermia, and we observed no significant differences in reported adverse events between hypothermia and control groups. Overall the quality of the evidence was moderate (pneumonia) to low (hypokalaemia).
Authors' conclusions
Evidence of moderate quality suggests that conventional cooling methods provided to induce mild therapeutic hypothermia improve neurological outcome after cardiac arrest, specifically with better outcomes than occur with no temperature management. We obtained available evidence from studies in which the target temperature was 34°C or lower. This is consistent with current best medical practice as recommended by international resuscitation guidelines for hypothermia/targeted temperature management among survivors of cardiac arrest. We found insufficient evidence to show the effects of therapeutic hypothermia on participants with in‐hospital cardiac arrest, asystole or non‐cardiac causes of arrest.
Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence ...suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published. This review was originally published in 2009.
We performed a systematic review and meta-analysis to assess the effectiveness of therapeutic hypothermia in patients after cardiac arrest. Neurologic outcome, survival and adverse events were our main outcomes. We aimed to perform individual patient data analysis, if data were available, and to form subgroups according to the cardiac arrest situation.
We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2001, Issue 7); MEDLINE (1971 to July 2011); EMBASE (1987 to July 2011); CINAHL (1988 to July 2011); PASCAL (2000 to July 2011); and BIOSIS (1989 to July 2011). The original search was performed in January 2007.
We included all randomized controlled trials assessing the effectiveness of therapeutic hypothermia in patients after cardiac arrest, without language restrictions. Studies were restricted to adult populations cooled with any cooling method, applied within six hours of cardiac arrest.
Validity measures, the intervention, outcomes and additional baseline variables were entered into a database. Meta-analysis was only done for a subset of comparable studies with negligible heterogeneity. For these studies, individual patient data were available.
We included four trials and one abstract reporting on 481 patients in the systematic review. The updated search resulted in no new studies to include. Quality of the included studies was good in three out of five studies. For the three comparable studies on conventional cooling methods all authors provided individual patient data. With conventional cooling methods, patients in the hypothermia group were more likely to reach a best cerebral performance categories (CPC) score of one or two (five point scale: 1 = good cerebral performance, to 5 = brain death) during the hospital stay (individual patient data; RR 1.55; 95% CI 1.22 to 1.96) and were more likely to survive to hospital discharge (individual patient data; RR 1.35; 95% CI 1.10 to 1.65) compared to standard post-resuscitation care. Across all studies, there was no significant difference in reported adverse events between hypothermia and control.
Conventional cooling methods to induce mild therapeutic hypothermia seem to improve survival and neurologic outcome after cardiac arrest. Our review supports the current best medical practice as recommended by the International Resuscitation Guidelines.
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NUK, OILJ, UL, UM, UPUK, VSZLJ
Recently 2 randomized trials in comatose survivors of cardiac arrest documented that therapeutic hypothermia improved neurological recovery. The narrow inclusion criteria resulted in an international ...recommendation to cool only a restricted group of primary cardiac arrest survivors. In this retrospective cohort study we investigated the efficacy and safety of endovascular cooling in unselected survivors of cardiac arrest.
Consecutive comatose survivors of cardiac arrest, who were either cooled for 24 hours to 33 degrees C with endovascular cooling or treated with standard postresuscitation therapy, were analyzed. Complication data were obtained by retrospective chart review.
Patients in the endovascular cooling group had 2-fold increased odds of survival (67/97 patients versus 466/941 patients; odds ratio 2.28, 95% CI, 1.45 to 3.57; P<0.001). After adjustment for baseline imbalances the odds ratio was 1.96 (95% CI, 1.19 to 3.23; P=0.008). When discounting the observational data in a Bayesian analysis by using a sceptical prior the posterior odds ratio was 1.61 (95% credible interval, 1.06 to 2.44). In the endovascular cooling group, 51/97 patients (53%) survived with favorable neurology as compared with 320/941 (34%) in the control group (odds ratio 2.15, 95% CI, 1.38 to 3.35; P=0.0003; adjusted odds ratio 2.56, 1.57 to 4.17). There was no difference in the rate of complications except for bradycardia.
Endovascular cooling improved survival and short-term neurological recovery compared with standard treatment in comatose adult survivors of cardiac arrest. Temperature control was effective and safe with this device.
CONTEXT Arterial puncture closing devices (APCDs) were developed to replace
standard compression at the puncture site and to shorten bed rest following
percutaneous coronary intervention. OBJECTIVE ...To assess the safety and efficacy of APCDs (Angioseal, Vasoseal, Duett,
Perclose, Techstar, Prostar) compared with standard manual compression in
patients undergoing coronary angiography or percutaneous vascular interventions. DATA SOURCES A systematic literature search of MEDLINE (1966-January 2003), EMBASE
(1989-January 2003), PASCAL (1996-January 2003), BIOSIS (1990-January 2003),
and CINHAL (1982-January 2003) databases and the Cochrane Central Register
of Controlled Trials for relevant articles in any language. STUDY SELECTION Included randomized controlled trials reporting vascular complications
at the puncture site (hematoma, bleeding, arteriovenous fistula, pseudoaneurysm)
and efficacy (time to hemostasis, time to ambulation, time to discharge from
hospital). DATA EXTRACTION Two reviewers abstracted the data independently and in duplicate. Disagreements
were resolved by discussion among at least 3 reviewers. The most important
criteria were adequacy of allocation concealment, whether the analysis was
according to the intention-to-treat principle, and if person assessing the
outcome was blinded to intervention group. Random-effects models were used
to pool the data. DATA SYNTHESIS Thirty trials met the selection criteria and included up to 4000 patients.
When comparing any APCD with standard compression, the relative risk (RR)
of groin hematoma was 1.14 (95% confidence interval CI, 0.86-1.51; P = .35); bleeding, 1.48 (95% CI, 0.88-2.48; P = .14); developing an arteriovenous fistula, 0.83 (95% CI, 0.23-2.94; P = .77); and developing a pseudoaneurysm at the puncture
site, 1.19 (95% CI, 0.75-1.88; P = .46). Time to
hemostasis was shorter in the group with APCD compared with standard compression
(mean difference, 17 minutes; range, 14-19 minutes), but there was a high
degree of heterogeneity among studies. Only 2 studies explicitly reported
allocation concealment, blinded outcome assessment, and intention-to-treat
analysis. When limiting analyses to only trials that used explicit intention-to-treat
approaches, APCDs were associated with a higher risk of hematoma (RR, 1.89;
95% CI, 1.13-3.15) and a higher risk of pseudoaneurysm (RR, 5.40; 95% CI,
1.21-24.5). CONCLUSIONS Based on this meta-analysis of 30 randomized trials, many of poor methodological
quality, there is only marginal evidence that APCDs are effective and there
is reason for concern that these devices may increase the risk of hematoma
and pseudoaneurysm.
OBJECTIVE:Only a few patients survive cardiac arrest with favorable neurologic recovery. Our objective was to assess whether induced hypothermia improves neurologic recovery in survivors of primary ...cardiac arrest.
DATA SOURCE:Studies were identified by a computerized search of MEDLINE, EMBASE, CINAHL, PASCAL, the Cochrane Controlled Trial Register, and BIOSIS.
STUDY SELECTION:We included randomized and quasi-randomized, controlled trials of adults who were successfully resuscitated, where therapeutic hypothermia was applied within 6 hrs after arrival at the emergency department and where the neurologic outcome was compared. We excluded studies without a control group and studies with historical controls.
DATA EXTRACTION:All authors of the identified trials supplied individual patient data with a predefined set of variables.
DATA SYNTHESIS:We identified three randomized trials. The analyses were conducted according to the intention-to-treat principle. Summary odds ratios were calculated using a random effects model and translated into risk ratios. More patients in the hypothermia group were discharged with favorable neurologic recovery (risk ratio, 1.68; 95% confidence interval, 1.29–2.07). The 95% confidence interval of the number-needed-to-treat to allow one additional patient to leave the hospital with favorable neurologic recovery was 4–13. One study followed patients to 6 months or death. Being alive at 6 months with favorable functional neurologic recovery was more likely in the hypothermia group (risk ratio, 1.44; 95% confidence interval, 1.11–1.76).
CONCLUSIONS:Mild therapeutic hypothermia improves short-term neurologic recovery and survival in patients resuscitated from cardiac arrest of presumed cardiac origin. Its long-term effectiveness and feasibility at an organizational level need further research.
Female patients and patients with a lower level socioeconomic status (SES) often experience less favorable health outcomes. We aimed to investigate whether gender and socioeconomic status of patients ...with acute ischemic stroke or transient ischemic attack are associated with different diagnostic and treatment strategies.
The risk factors of interest were gender and SES. We predefined our diagnostic and treatment end points according to current stroke guidelines and used multivariate models to adjust for age, stroke severity, and comorbidities.
A total of 2606 patients were included in the analysis. Women were less likely to receive antiplatelet agents within the first 48 hours after admission (OR: 0.59, 95% CI: 0.53 to 0.89) and more likely to have their blood glucose measured on admission than men (OR: 1.52, 95% CI: 1.1 to 2.1). With higher SES patients were more likely to receive a TTE or TTE during hospital stay. Women were almost twice as likely to receive a prescription for antidepressants at discharge OR of 1.96 (95% CI: 1.48 to 2.59).
Socioeconomic status and gender are associated with some diagnostic and treatment differences of acute ischemic stroke. Most pronounced were a reduced chance for women to receive antiplatelet therapy on admission and a reduced chance for a TTE and TEE with a lower level of SES, whereas the rate of thrombolysis was unbiased by gender and SES.
Osteoarthritis of the knee affects up to 10% of the elderly population. The condition is frequently treated by intra-articular injection of hyaluronic acid. We performed a systematic review and ...meta-analysis of randomized controlled trials to assess the effectiveness of this treatment.
We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane Controlled Trial Register from inception until April 2004 using a combination of search terms for knee osteoarthritis and hyaluronic acid and a filter for randomized controlled trials. We extracted data on pain at rest, pain during or immediately after movement, joint function and adverse events.
Twenty-two trials that reported usable quantitative information on any of the predefined end points were identified and included in the systematic review. Even though pain at rest may be improved by hyaluronic acid, the data available from these studies did not allow an appropriate assessment of this end point. Patients who received the intervention experienced a reduction in pain during movement: the mean difference on a 100-mm visual analogue scale was -3.8 mm (95% confidence interval CI -9.1 to 1.4 mm) after 2-6 weeks, -4.3 mm (95% CI -7.6 to -0.9 mm) after 10-14 weeks and -7.1 mm (95% CI -11.8 to -2.4 mm) after 22-30 weeks. However, this effect was not compatible with a clinically meaningful difference (expected to be about 15 mm on the visual analogue scale). Furthermore, the effect was exaggerated by trials not reporting an intention-to-treat analysis. No improvement in knee function was observed at any time point. Even so, the effect of hyaluronic acid on knee function was more favourable when allocation was not concealed. Adverse events occurred slightly more often among patients who received the intervention (relative risk 1.08, 95% CI 1.01 to 1.15). Only 4 trials explicitly reported allocation concealment, had blinded outcome assessment and presented intention-to-treat data.
According to the currently available evidence, intra-articular hyaluronic acid has not been proven clinically effective and may be associated with a greater risk of adverse events. Large trials with clinically relevant and uniform end points are necessary to clarify the benefit-risk ratio.
Background and Purpose —Recent animal studies showed that mild resuscitative hypothermia improves neurological outcome when applied after cardiac arrest. In a 3-year randomized, prospective, ...multicenter clinical trial, we hypothesized that mild resuscitative cerebral hypothermia (32°C to 34°C core temperature) would improve neurological outcome after cardiac arrest. Methods —We lowered patients’ temperature after admission to the emergency department and continued cooling for at least 24 hours after arrest in conjunction with advanced cardiac life support. The cooling technique chosen was external head and total body cooling with a cooling device in conjunction with a blanket and a mattress. Infrared tympanic thermometry was monitored before a central pulmonary artery thermistor probe was inserted. Results —In 27 patients (age 58 interquartile range IQR 52 to 64 years; 7 women; estimated “no-flow” duration 6 IQR 1 to 11 minutes and “low-flow” duration 15 IQR 9 to 23 minutes; admitted to the emergency department 36 IQR 24 to 43 minutes after return of spontaneous circulation), we could initiate cooling within 62 (IQR 41 to 75) minutes and achieve a pulmonary artery temperature of 33±1°C 287 (IQR 42 to 401) minutes after cardiac arrest. During 24 hours of mild resuscitative hypothermia, no major complications occurred. Passive rewarming >35°C was accomplished within 7 hours. Conclusions —Mild resuscitative hypothermia in patients is feasible and safe. A clinical multicenter trial might prove that mild hypothermia is a useful method of cerebral resuscitation after global ischemic states.
OBJECTIVE:To assess survival in cancer patients admitted to an intensive care unit (ICU) with respect to the nature of malignancy, cause of ICU admittance, and course during ICU stay as well as to ...evaluate the prognostic value of the Acute Physiology and Chronic Health Evaluation (APACHE) III score.
DESIGN:Retrospective cohort study.
SETTING:ICU at a university cancer referral center.
PATIENTS:A total of 414 cancer patients admitted to the ICU during a period of 66 months.
INTERVENTIONS:None.
MEASUREMENTS:Charts of the patients were analyzed with respect to underlying disease, cause of admission, APACHE III score, need and duration of mechanical ventilation, neutropenia and development of septic shock, as well as ICU survival and survival after discharge. Mortality data were compared with two control groups1362 patients admitted to our ICU suffering from diseases other than cancer and 2,776 cancer patients not admitted to the ICU.
MAIN RESULTS:ICU survival was 53%, and 1-yr survival was 23%. The 1-yr mortality rate was significantly lower in both control groups. Patients admitted after bone marrow transplantation had the highest mortality. In a multivariate analysis, prognosis was negatively influenced by respiratory insufficiency, the need of mechanical ventilation, and development of septic shock during the ICU stay. Admission after cardiopulmonary resuscitation yielded high ICU mortality but a relatively good long-term prognosis. Admission after surgery and as a result of acute hemorrhage was associated with a good prognosis. Age, neutropenia, and underlying disease did not influence outcome significantly. Admission APACHE III scores were significantly higher in nonsurvivors but failed to predict individual outcome satisfactorily. All patients with APACHE III scores of >80 died at the ICU.
CONCLUSION:A combination of factors must be taken into account to estimate a critically ill cancer patient's prognosis in the ICU. The APACHE III scoring system alone should not be used to make decisions about therapy prolongation. Admission to the ICU worsens the prognosis of a cancer patient substantially; however, as ICU mortality is 47%, comparable with severely ill noncancer patients, general reluctance to admit cancer patients to an ICU does not seem to be justified.
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