Jesper Kjaergaard

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.).

Right ventricular dysfunction as an independent predictor of short‐ and long‐term mortality in patients with heart failure

The prognostic importance of right ventricular (RV) dysfunction in heart failure (HF) has been suggested in patients with severe systolic heart failure. Tricuspid annular plane systolic excursion (TAPSE) is a simple echocardiographic measure of RV ejection fraction, but may be affected by co‐existing chronic obstructive pulmonary disease (COPD).

Detection of Pulmonary Embolism with Combined Ventilation–Perfusion SPECT and Low-Dose CT: Head-to-Head Comparison with Multidetector CT Angiography

The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer testing, and imaging with either pulmonary ventilation–perfusion (V/Q) scintigraphy or pulmonary multidetector CT (MDCT) angiography. Both V/Q SPECT and MDCT angiography seem to have high diagnostic accuracy. However, only limited data directly comparing these 2 modalities are available. Hybrid γ-camera/MDCT systems have been introduced and allow simultaneous 3-dimensional lung V/Q SPECT and MDCT angiography, suitable for diagnosing PE. The aim of our study was to compare, in a prospective design, the diagnostic ability of V/Q SPECT, V/Q SPECT combined with low-dose CT, and pulmonary MDCT angiography obtained simultaneously using a combined SPECT/MDCT scanner in patients suspected of having PE. Methods: Consecutive patients from June 2006 to February 2008 suspected of having acute PE were referred to the Department of Nuclear Medicine at Rigshospitalet or Frederiksberg Hospital, Denmark, for V/Q SPECT as a first-line imaging procedure. The number of eligible patients was 196. Patients with positive D-dimer results (>0.5 mmol/mL) or a clinical assessment with a Wells score greater than 2 were included and underwent V/Q SPECT, low-dose CT, and pulmonary MDCT angiography in a single session. Patient follow-up was 6 mo. Results: A total of 81 simultaneous studies were available for analysis, of which 38% were from patients with PE. V/Q SPECT had a sensitivity of 97% and a specificity of 88%. When low-dose CT was added, the sensitivity was still 97% and the specificity increased to 100%. Perfusion SPECT with low-dose CT had a sensitivity of 93% and a specificity of 51%. MDCT angiography alone had a sensitivity of 68% and a specificity of 100%. Conclusion: We conclude that V/Q SPECT in combination with low-dose CT without contrast enhancement has an excellent diagnostic performance and should therefore probably be considered first-line imaging in the work-up of PE in most cases.

The impact of therapeutic hypothermia on neurological function and quality of life after cardiac arrest

AIMS To assess the impact of therapeutic hypothermia on cognitive function and quality of life in comatose survivors of out of Hospital Cardiac arrest (OHCA). METHODS We prospectively studied comatose survivors of OHCA consecutively admitted in a 4-year period. Therapeutic hypothermia was implemented in the last 2-year period, intervention period (n=79), and this group was compared to patients admitted the 2 previous years, control period (n=77). We assessed Cerebral Performance Category (CPC), survival, Mini Mental State Examination (MMSE) and self-rated quality of life (SF-36) 6 months after OHCA in the subgroup with VF/VT as initial rhythm. RESULTS CPC in patients alive at hospital discharge was significantly better in the intervention period with a CPC of 1-2 in 97% vs. 71% in the control period, p=0.003, corresponding to an adjusted odds ratio of a favourable cerebral outcome of 17, p=0.01. No significant differences were found in long-term survival (57% vs. 56% alive at 30 months), MMSE, or SF-36. Therapeutic hypothermia (hazard ratio: 0.15, p=0.007) and bystander CPR (hazard ratio 0.19, p=0.002) were significantly related to survival in the intervention period. CONCLUSION CPC at discharge from hospital was significantly improved following implementation of therapeutic hypothermia in comatose patients resuscitated from OCHA with VF/VT. However, significant improvement in survival, cognitive status or quality of life could not be detected at long-term follow-up.

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.

Prevalence, predictors, and survival in pulmonary hypertension related to end-stage chronic obstructive pulmonary disease

BACKGROUND The prevalence, prognostic importance, and factors that predict the presence and degree of pulmonary hypertension (PH) diagnosed with right heart catheterization (RHC) in patients with end-stage chronic obstructive pulmonary disease (COPD) remain unclear. METHODS This retrospective study included 409 patients (61% women) with COPD/emphysema or α-1-antitrypsin deficiency who underwent lung transplant evaluation during 1991 to 2010. We analyzed the occurrence and degree of PH and compared demographics, oxygenation, lung function, hemodynamics, functional capacity, and survival in patients with and without PH. Prediction of PH was assessed using univariate and multivariate regression analysis. RESULTS The mean age at evaluation was 54 ± 7 years. All patients were in New York Heart Association functional class III-IV, with forced expiratory volume in 1 second of 23% ± 7% and total lung capacity of 126% ± 21% of predicted. PH was present in 146 (36%). The analysis excluded 53 (13%) with pulmonary venous hypertension (PVH). The distribution of the mean pulmonary artery pressure (mPAP) in patients with or without PH showed a unimodal normally distributed population, with a mean of 23.8 ± 6.0 mm Hg. Predictors of PH were partial pressures of oxygen and carbon dioxide. The 5-year survival rate was 37% in COPD patients with PH vs 63% in patients without PH (p = 0.016). Survival after lung transplantation did not differ (p = 0.37). CONCLUSIONS RHC verified PH in 36% of COPD patients. Hypoxemia and hypercapnia were associated with mPAP. PH is associated with worse survival in COPD, but PH does not influence the prognosis after lung transplantation.

Chronic obstructive pulmonary disease in patients admitted with heart failure

Objective.  Chronic obstructive pulmonary disease (COPD) is an important differential diagnosis in patients with heart failure (HF). The primary aims were to determine the prevalence of COPD and to test the accuracy of self‐reported COPD in patients admitted with HF. Secondary aims were to study a possible relationship between right and left ventricular function and pulmonary function.

Post-hypothermia fever is associated with increased mortality after out-of-hospital cardiac arrest

OBJECTIVE Post-cardiac arrest fever has been associated with adverse outcome before implementation of therapeutic hypothermia (TH), however the prognostic implications of post-hypothermia fever (PHF) in the era of modern post-resuscitation care including TH has not been thoroughly investigated. The aim of the study was to assess the prognostic implication of PHF in a large consecutive cohort of comatose survivors after out-of-hospital cardiac arrest (OHCA) treated with TH. METHODS In the period 2004-2010, a total of 270 patients resuscitated after OHCA and surviving a 24-h protocol of TH with a target temperature of 32-34°C were included. The population was stratified in two groups by median peak temperature (≥38.5°C) within 36h after rewarming: PHF and no-PHF. Primary endpoint was 30-days mortality and secondary endpoint was neurological outcome assessed by Cerebral Performance Category (CPC) at hospital discharge. RESULTS PHF (≥38.5°C) was associated with a 36% 30-days mortality rate compared to 22% in patients without PHF, plog-rank=0.02, corresponding to an adjusted hazard rate (HR) of 1.8 (95% CI: 1.1-2.7), p=0.02). The maximum temperature (HR=2.0 per °C above 36.5°C (95% CI: 1.4-3.0), p=0.0005) and the duration of PHF (HR=1.6 per 8h (95% CI: 1.3-2.0), p<0.0001) were also independent predictors of 30-days mortality in multivariable models. Good neurological outcome (CPC1-2) versus unfavourable outcome (CPC3-5) at hospital discharge was found in 61% vs. 39% in the PHF group compared to 75% vs. 25% in the No PHF group, p=0.02. CONCLUSIONS Post-hypothermia fever ≥38.5°C is associated with increased 30-days mortality, even after controlling for potential confounding factors. Avoidance of PHF as a therapeutic target should be evaluated in prospective randomized trials.

The prognostic importance of lung function in patients admitted with heart failure

The purpose of the present study was to determine the prognostic importance for all‐cause mortality of lung function variables obtained by spirometry in an unselected group of patients admitted with heart failure (HF).

Neurologic Function and Health-Related Quality of Life in Patients Following Targeted Temperature Management at 33°C vs 36°C After Out-of-Hospital Cardiac Arrest A Randomized Clinical Trial

IMPORTANCE Brain injury affects neurologic function and quality of life in survivors after cardiac arrest. OBJECTIVE To compare the effects of 2 target temperature regimens on long-term cognitive function and quality of life after cardiac arrest. DESIGN, SETTING, AND PARTICIPANTS In this multicenter, international, parallel group, assessor-masked randomized clinical trial performed from November 11, 2010, through January 10, 2013, we enrolled 950 unconscious adults with cardiac arrest of presumed cardiac cause from 36 intensive care units in Europe and Australia. Eleven patients were excluded from analysis for a total sample size of 939. INTERVENTIONS Targeted temperature management at 33°C vs 36°C. MAIN OUTCOMES AND MEASURES Cognitive function was measured by the Mini-Mental State Examination (MMSE) and assessed by observers through the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Patients reported their activities in daily life and mental recovery through Two Simple Questions and their quality of life through the Medical Outcomes Study 36-Item Short Form Health Survey, version 2. RESULTS In the modified intent-to-treat population, including nonsurvivors, the median MMSE score was 14 in the 33°C group (interquartile range [IQR], 0-28) vs 17 in the 36°C group (IQR, 0-29) (P = .77), and the IQCODE score was 115 (IQR, 79-130) vs 115 (IQR, 80-130) (P = .57) in the 33°C and 36°C groups, respectively. The median MMSE score for survivors was within the reference range and similar (33°C group median, 28; IQR, 26-30; vs 36°C group median, 28; IQR, 25-30; P = .61). The median IQCODE score was within the minor deficit range (33°C group median, 79.5; IQR, 78.0-85.9; vs 36°C group median, 80.7; IQR, 78.0-86.9; P = .04). A total of 18.8% vs 17.5% of survivors reported needing help with everyday activities (P = .71), and 66.5% in the 33°C group vs 61.8% in the 36°C group reported that they thought they had made a complete mental recovery (P = .32). The mean (SD) mental component summary score was 49.1 (12.5) vs 49.0 (12.2) (P = .79), and the mean (SD) physical component summary score was 46.8 (13.8) and 47.5 (13.8) (P = .45), comparable to the population norm. CONCLUSIONS AND RELEVANCE Quality of life was good and similar in patients with cardiac arrest receiving targeted temperature management at 33°C or 36°C. Cognitive function was similar in both intervention groups, but many patients and observers reported impairment not detected previously by standard outcome scales. TRIAL REGISTRATION ClinicalTrials.gov NCT01020916.