Jørund Langørgen

Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest

BACKGROUND Unconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. METHODS In an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33°C or 36°C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. RESULTS In total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33°C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36°C group (225 of 466 patients) (hazard ratio with a temperature of 33°C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33°C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36°C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. CONCLUSIONS In unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33°C did not confer a benefit as compared with a targeted temperature of 36°C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.).

Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design

BACKGROUND Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32°C to 34°C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. METHODS The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33°C or 36°C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. DISCUSSION The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.

Factors predicting the use of therapeutic hypothermia and survival in unconscious out-of-hospital cardiac arrest patients admitted to the ICU

IntroductionTherapeutic hypothermia (TH) after out-of-hospital cardiac arrest (OHCA) was adopted early in Norway. Since 2004 the general recommendation has been to cool all unconscious OHCA patients treated in the intensive care unit (ICU), but the decision to cool individual patients was left to the responsible physician. We assessed factors that were associated with use of TH and predicted survival.MethodWe conducted a retrospective observational study of prospectively collected cardiac arrest and ICU registry data from 2004 to 2008 at three university hospitals.ResultsA total of 715 unconscious patients older than 18 years of age, who suffered OHCA of both cardiac and non-cardiac causes, were included. With an overall TH use of 70%, the survival to discharge was 42%, with 90% of the survivors having a favourable cerebral outcome. Known positive prognostic factors such as witnessed arrest, bystander cardio pulmonary resuscitation (CPR), shockable rhythm and cardiac origin were all positive predictors of TH use and survival. On the other side, increasing age predicted a lower utilisation of TH: Odds Ratio (OR), 0.96 (95% CI, 0.94 to 0.97); as well as a lower survival: OR 0.96 (95% CI, 0.94 to 0.97). Female gender was also associated with a lower use of TH: OR 0.65 (95% CI, 0.43 to 0.97); and a poorer survival: OR 0.57 (95% CI, 0.36 to 0.92). After correcting for other prognostic factors, use of TH remained an independent predictor of improved survival with OR 1.91 (95% CI 1.18-3.06; P <0.001). Analysing subgroups divided after initial rhythm, these effects remained unchanged for patients with shockable rhythm, but not for patients with non-shockable rhythm where use of TH and female gender lost their predictive value.ConclusionsAlthough TH was used in the majority of unconscious OHCA patients admitted to the ICU, actual use varied significantly between subgroups. Increasing age predicted both a decreased utilisation of TH as well as lower survival. Further, in patients with a shockable rhythm female gender predicted both a lower use of TH and poorer survival. Our results indicate an underutilisation of TH in some subgroups. Hence, more research on factors affecting TH use and the associated outcomes in subgroups of post-resuscitation patients is needed.

Capillary leakage in post-cardiac arrest survivors during therapeutic hypothermia - a prospective, randomised study

BackgroundFluids are often given liberally after the return of spontaneous circulation. However, the optimal fluid regimen in survivors of cardiac arrest is unknown. Recent studies indicate an increased fluid requirement in post-cardiac arrest patients. During hypothermia, animal studies report extravasation in several organs, including the brain. We investigated two fluid strategies to determine whether the choice of fluid would influence fluid requirements, capillary leakage and oedema formation.Methods19 survivors with witnessed cardiac arrest of primary cardiac origin were allocated to either 7.2% hypertonic saline with 6% poly (O-2-hydroxyethyl) starch solution (HH) or standard fluid therapy (Ringers Acetate and saline 9 mg/ml) (control). The patients were treated with the randomised fluid immediately after admission and continued for 24 hours of therapeutic hypothermia.ResultsDuring the first 24 hours, the HH patients required significantly less i.v. fluid than the control patients (4750 ml versus 8010 ml, p = 0.019) with comparable use of vasopressors. Systemic vascular resistance was significantly reduced from 0 to 24 hours (p = 0.014), with no difference between the groups. Colloid osmotic pressure (COP) in serum and interstitial fluid (p < 0.001 and p = 0.014 respectively) decreased as a function of time in both groups, with a more pronounced reduction in interstitial COP in the crystalloid group. Magnetic resonance imaging of the brain did not reveal vasogenic oedema.ConclusionsPost-cardiac arrest patients have high fluid requirements during therapeutic hypothermia, probably due to increased extravasation. The use of HH reduced the fluid requirement significantly. However, the lack of brain oedema in both groups suggests no superior fluid regimen. Cardiac index was significantly improved in the group treated with crystalloids. Although we do not associate HH with the renal failures that developed, caution should be taken when using hypertonic starch solutions in these patients.Trial registrationNCT00347477.

Short-term and long-term case fatality in 11 878 patients hospitalized with a first acute myocardial infarction, 1979-2001: the Western Norway cardiovascular registry

Background Few studies have direct estimates of long-term survival after acute myocardial infarction (AMI). Our objective was to provide such estimates, and trends in these estimates, using data from a single hospital over a 23-year period. Design A retrospective cohort study. Methods We examined 28-day, 1-year and 10-year case fatality among 7635 men and 4243 women admitted to Haukeland University Hospital with a first AMI, during 1979-2001. Information on cardiovascular diagnoses and procedures were registered in the Western Norway Cardiovascular Registry, and data on deaths were obtained from the Cause of Death Registry, Statistics Norway. Results From 1979-1985 to 1994-2001, crude 28-day case fatality declined from 31.1 to 19.8% in men and from 37.3 to 26.8% in women (both, P-trend < 0.0001). Crude 10-year case fatality declined from 69.5-55.5% in men and from 80.8-66.1% in women (both, P-trend < 0.0001). Landmark analysis showed a decline in 1-10-year case fatality, among patients less than 60 years of age from 26.1 to 13.8% in men, and from 33.3 to 6.4% in women. In patients ≥ 60 years, the 28-day, 1-year and 10-year age-adjusted case-fatality rates were significantly lower in women than men. Conclusion Landmark analysis showed substantial improvement in up to 10 years survival after hospitalization for a first AM I. A significantly lower age-adjusted case fatality in women ≥ 60 years already after 28 days compared with men is specifically noticed.

Cognitive function and health-related quality of life four years after cardiac arrest

AIM Neuropsychological testing has uncovered cognitive impairment in cardiac arrest survivors with good neurologic outcome according to the cerebral performance categories. We investigated cognitive function and health-related quality of life four years after cardiac arrest. METHODS Thirty cardiac arrest survivors over the age of 18 in cerebral performance category 1 or 2 on hospital discharge completed the EQ-5D-5L and HADS questionnaires prior to cognitive testing using the Cambridge Neuropsychological Test Automated Battery. The results were compared with population norms. RESULTS Twenty-nine per cent of patients were cognitively impaired. The pattern of cognitive impairment reflects dysfunction in the medial temporal lobe, with impaired short-time memory and executive function slightly but distinctly affected. There was a significant reduction in quality of life on the EQ-VAS, but not on the EQ index. CONCLUSION Cognitive impairment four years after cardiac arrest affected more than one quarter of the patients. Short-term memory was predominantly affected.

Evaluation of the appropriateness and outcome of in-hospital telemetry monitoring.

The American Heart Association classifies monitored patients into 3 categories. The aims of this study were to (1) investigate how patients are assigned according to the American Heart Association classification, (2) determine the number and type of arrhythmic events experienced by these patients, and (3) describe subsequent changes in management. A prospective observational study design was used. All patients assigned to telemetry during a 3-month period were consecutively enrolled in our study. Data were collected 24/7. Only arrhythmias that might require a change in management were recorded. Monitor watchers at the central monitoring station completed a standard data sheet assessing 64 variables. These data, as well as medical records, were reviewed by the investigator. Overall, 1,194 patients were included. Eighteen percent of the patients were assigned to American Heart Association class I (monitoring indicated), 71% to class II (monitoring may be of benefit), and 11% to class III (monitoring not indicated). The overall arrhythmia event rate was 33%. Forty-three percent of class I patients, 28% of class II patients, and 47% of class III patients experienced arrhythmia events. Change in management occurred in 25% of class I patients, 14% of class II patients, and 29% of class III patients. Although the number of class III indications should have been reduced, nearly 1/2 of class III patients experienced arrhythmia events and 1/3 of them received management changes. This outcome challenges existing guidelines. In conclusion, most patients in this study were monitored appropriately, according to class I and II indications.

Implications of changing definitions of myocardial infarction on number of events and all-cause mortality: the WHO 1979, ESC/ACC 2000, AHA 2003, and Universal 2007 definitions revisited:

Purpose To analyse the impact of four different definitions of acute myocardial infarction (AMI) on number of events and all-cause mortality after AMI. Methods We retrospectively examined number of AMI events and mortality according to four different definitions of AMI, among 1494 patients admitted to Haukeland University Hospital in Norway from March 2002 to February 2003. Eligible for analysis were 815 patients with a discharge diagnosis of an AMI, and 679 patients without any AMI discharge diagnosis but with elevated cardiac troponin I level during admission. Results Applying the WHO 1979 definition resulted in 566 definite AMIs among the 1494 patients and was used as reference. According to the other definitions, there were 455 (−20%) definite AMIs by the original troponin ‘rise and fall’ version of the ESC/ACC 2000 definition, 729 (+29%) by the troponin ‘rise or fall’ interpretation of the ESC/ACC 2000 definition, 761 (+34%) by the AHA 2003 definition, and 743 (+31%) by the Universal 2007 definition (all p < 0.001). The 28-day, 1-year, 5-year, and 8-year mortality for definite AMI applying the WHO 1979 definition was 12, 19, 32, and 40%, whereas applying the Universal 2007 definition resulted in a mortality of 14, 21, 35, and 43%, respectively. Conclusions The change of definitions of AMI during the last decades has had a significant impact on the number of AMI events and a moderate impact on the AMI mortality among hospitalized patients.

Should patients who use illicit drugs be offered a second heart-valve replacement?

Intravenous drug users (IVDUs) have an elevated risk of contracting infectious endocarditis. Most of them have good effect from medical treatment, but some will need valve replacement. Until a few years ago, our hospital withheld valve surgery if patients with intravenous drug dependency and infectious endocarditis came to need a second valve replacement. However, there are no consensus guidelines for treatment of this group of patients, and a dearth of data on the effects and benefits of interventions. Using a method of ethical analysis, we here discuss whether it is appropriate to offer valve surgery to drug users for a second time.

The universal 2012 definition of myocardial infarction compared to the 2007 definition.

Abstract Objectives: The third Universal 2012 definition of myocardial infarction (MI) has not been compared to the Universal 2007 definition with regard to the number of cases identified, classification and mortality. Design: We examined potential MI events according to the two universal definitions in 1494 patients admitted to the University hospital during the 12 months. Patients were included either because of an MI discharge diagnosis (815 patients) or due to elevated troponin I levels without an MI discharge diagnosis (679 patients). Results: Applying the Universal 2012 definition resulted in 760 of the 1494 patients suffering from MI, as compared to 769 according to the Universal 2007 definition. The lower number of MI events applying the 2012 definition was mainly explained by the stricter definition of Type 4a MI. The 760 MI events were classified as Type 1 (685), 2 (27), 3 (28), 4a (13), 4b (3) and 5 (4). Conclusions: The application of the third Universal 2012 definition of MI instead of the Universal 2007 definition resulted in a 1% reduction of the total number of MIs. For a practical clinical purpose, the reduction was confined to patients with Type 4a MI. The change of definition had no impact on all-cause mortality.