Outcomes of mild-to-moderate postresuscitation shock after non-shockable cardiac arrest and association with temperature management: a post hoc analysis of HYPERION trial data.

BACKGROUND: Outcomes of postresuscitation shock after cardiac arrest can be affected by targeted temperature management (TTM). A post hoc analysis of the "TTM1 trial" suggested higher mortality with hypothermia at 33 °C. We performed a post hoc analysis of HYPERION trial data to assess potential associations linking postresuscitation shock after non-shockable cardiac arrest to hypothermia at 33 °C on favourable functional outcome. METHODS: We divided the patients into groups with vs. without postresuscitation (defined as the need for vasoactive drugs) shock then assessed the proportion of patients with a favourable functional outcome (day-90 Cerebral Performance Category [CPC] 1 or 2) after hypothermia (33 °C) vs. controlled normothermia (37 °C) in each group. Patients with norepinephrine or epinephrine > 1 µg/kg/min were not included. RESULTS: Of the 581 patients included in 25 ICUs in France and who did not withdraw consent, 339 had a postresuscitation shock and 242 did not. In the postresuscitation-shock group, 159 received hypothermia, including 14 with a day-90 CPC of 1-2, and 180 normothermia, including 10 with a day-90 CPC of 1-2 (8.81% vs. 5.56%, respectively; P = 0.24). After adjustment, the proportion of patients with CPC 1-2 also did not differ significantly between the hypothermia and normothermia groups (adjusted hazards ratio, 1.99; 95% confidence interval, 0.72-5.50; P = 0.18). Day-90 mortality was comparable in these two groups (83% vs. 86%, respectively; P = 0.43). CONCLUSIONS: After non-shockable cardiac arrest, mild-to-moderate postresuscitation shock at intensive-care-unit admission did not seem associated with day-90 functional outcome or survival. Therapeutic hypothermia at 33 °C was not associated with worse outcomes compared to controlled normothermia in patients with postresuscitation shock. Trial registration ClinicalTrials.gov, NCT01994772.

Targeted Temperature Management After In-Hospital Cardiac Arrest: An Ancillary Analysis of Targeted Temperature Management for Cardiac Arrest With Nonshockable Rhythm Trial Data.

BACKGROUND: Targeted temperature management (TTM) currently is the only treatment with demonstrated efficacy in attenuating the harmful effects on the brain of ischemia-reperfusion injury after cardiac arrest. However, whether TTM is beneficial in the subset of patients with in-hospital cardiac arrest (IHCA) remains unclear. RESEARCH QUESTION: Is TTM at 33 °C associated with better neurological outcomes after IHCA in a nonshockable rhythm compared with targeted normothermia (TN; 37 °C)? STUDY DESIGN AND METHODS: We performed a post hoc analysis of data from the published Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm randomized controlled trial in 584 patients. We included the 159 patients with IHCA; 73 were randomized to 33 °C treatment and 86 were randomized to 37 °C treatment. The primary outcome was survival with a good neurologic outcome (cerebral performance category [CPC] score of 1 or 2) on day 90. Mixed multivariate adjusted logistic regression analysis was performed to determine whether survival with CPC score of 1 or 2 on day 90 was associated with type of temperature management after adjustment on baseline characteristics not balanced by randomization. RESULTS: Compared with TN for 48 h, hypothermia at 33 °C for 24 h was associated with a higher percentage of patients who were alive with good neurologic outcomes on day 90 (16.4% vs 5.8%; P = .03). Day 90 mortality was not significantly different between the two groups (68.5% vs 76.7%; P = .24). By mixed multivariate analysis adjusted by Cardiac Arrest Hospital Prognosis score and circulatory shock status, hypothermia was associated significantly with good day 90 neurologic outcomes (OR, 2.40 [95% CI, 1.17-13.03]; P = .03). INTERPRETATION: Hypothermia at 33 °C was associated with better day 90 neurologic outcomes after IHCA in a nonshockable rhythm compared with TN. However, the limited sample size resulted in wide CIs. Further studies of patients after cardiac arrest resulting from any cause, including IHCA, are needed.

Insights from patients screened but not randomised in the HYPERION trial.

BACKGROUND: Few data are available about outcomes of patients screened for, but not enrolled in, randomised clinical trials. METHODS: We retrospectively reviewed patients who had non-inclusion criteria for the HYPERION trial comparing 33 °C to 37 °C in patients comatose after cardiac arrest in non-shockable rhythm, due to any cause. A good neurological outcome was defined as a day-90 Cerebral Performance Category score of 1 or 2. RESULTS: Of the 1144 patients with non-inclusion criteria, 1130 had day-90 information and, among these, 158 (14%) had good functional outcomes, compared to 7.9% overall in the HYPERION trial (10.2% with and 5.7% without hypothermia). Considerable centre-to-centre variability was found in the proportion of non-included patients who received hypothermia (0% to 83.8%) and who had good day-90 functional outcomes (0% to 31.3%). The proportion of patients with a good day-90 functional outcome was significantly higher with than without hypothermia (18.5% vs. 11.9%, P = 0.003). CONCLUSION: Our finding of better functional outcomes without than with inclusion in the HYPERION trial, despite most non-inclusion criteria being of adverse prognostic significance (e.g., long no-flow and low-flow times and haemodynamic instability), raises important questions about the choice of patient selection criteria and the applicability of trial results to everyday practice. At present, reserving hypothermia for patients without predictors of poor prognosis seems open to criticism.

Epidural analgesia in ICU chest trauma patients with fractured ribs: retrospective study of pain control and intubation requirements.

BACKGROUND: Nonintubated chest trauma patients with fractured ribs admitted to the intensive care unit (ICU) are at risk for complications and may require invasive ventilation at some point. Effective pain control is essential. We assessed whether epidural analgesia (EA) in patients with fractured ribs who were not intubated at ICU admission decreased the need for invasive mechanical ventilation (IMV). We also looked for risk factors for IMV. STUDY DESIGN AND METHODS: This retrospective, observational, multicenter study conducted in 40 ICUs in France included consecutive patients with three or more fractured ribs who were not intubated at admission between July 2013 and July 2015. RESULTS: Of the 974 study patients, 788 were included in the analysis of intubation predictors. EA was used in 130 (16.5%) patients, and 65 (8.2%) patients required IMV. Factors independently associated with IMV were chronic respiratory disease (P = 0.008), worse SAPS II (P < 0.0001), flail chest (P = 0.02), worse Injury Severity Score (P = 0.0003), higher respiratory rate at admission (P = 0.02), alcohol withdrawal syndrome (P < 0.001), and noninvasive ventilation (P = 0.04). EA was not associated with decreases in IMV requirements, median numerical rating scale pain score, or intravenous morphine requirements from day 1 to day 7. CONCLUSIONS: EA was not associated with a lower risk of IMV in chest trauma patients with at least 3 fractured ribs, moderate pain, and no intubation on admission. Further studies are needed to clarify the optimal pain control strategy in chest trauma patients admitted to the ICU, notably those with severe pain or high opioid requirements.

Targeted Temperature Management for Cardiac Arrest with Nonshockable Rhythm.

BACKGROUND: Moderate therapeutic hypothermia is currently recommended to improve neurologic outcomes in adults with persistent coma after resuscitated out-of-hospital cardiac arrest. However, the effectiveness of moderate therapeutic hypothermia in patients with nonshockable rhythms (asystole or pulseless electrical activity) is debated. METHODS: We performed an open-label, randomized, controlled trial comparing moderate therapeutic hypothermia (33°C during the first 24 hours) with targeted normothermia (37°C) in patients with coma who had been admitted to the intensive care unit (ICU) after resuscitation from cardiac arrest with nonshockable rhythm. The primary outcome was survival with a favorable neurologic outcome, assessed on day 90 after randomization with the use of the Cerebral Performance Category (CPC) scale (which ranges from 1 to 5, with higher scores indicating greater disability). We defined a favorable neurologic outcome as a CPC score of 1 or 2. Outcome assessment was blinded. Mortality and safety were also assessed. RESULTS: From January 2014 through January 2018, a total of 584 patients from 25 ICUs underwent randomization, and 581 were included in the analysis (3 patients withdrew consent). On day 90, a total of 29 of 284 patients (10.2%) in the hypothermia group were alive with a CPC score of 1 or 2, as compared with 17 of 297 (5.7%) in the normothermia group (difference, 4.5 percentage points; 95% confidence interval [CI], 0.1 to 8.9; P = 0.04). Mortality at 90 days did not differ significantly between the hypothermia group and the normothermia group (81.3% and 83.2%, respectively; difference, -1.9 percentage points; 95% CI, -8.0 to 4.3). The incidence of prespecified adverse events did not differ significantly between groups. CONCLUSIONS: Among patients with coma who had been resuscitated from cardiac arrest with nonshockable rhythm, moderate therapeutic hypothermia at 33°C for 24 hours led to a higher percentage of patients who survived with a favorable neurologic outcome at day 90 than was observed with targeted normothermia. (Funded by the French Ministry of Health and others; HYPERION ClinicalTrials.gov number, NCT01994772.).

Impact of a visual aid on discordance between physicians and family members about prognosis of critically ill patients.

OBJECTIVE: This study aimed to evaluate the impact of a visual aid on the discordance about prognosis between physicians and family members. METHODS: The study was performed in a general intensive care department with two 6-bed units. In the unit A, family members could consult a visual aid depicting day by day the evolution of global, hemodynamic, respiratory, renal and neurological conditions of the patient on a 10-point scale. In the unit B, they only received oral medical information. On day 7 of the ICU stay, the physician and family members estimated the prognosis of the patient among four proposals (life threatened; steady state but may worsen; steady state, should heal; will heal). Then we compared the rate of discordance about prognosis between physicians and family members in the two units. RESULTS: Seventy-nine consecutive patients admitted in the intensive care department and still present at day 7, their family members and physicians, were enrolled. Patients in the two units were comparable in age, sex ratio, reason for admission, SAPS II at admission and SOFA score at day 7. In the unit A, physician-family members discordance about prognosis occurred for 12 out of 39 patients (31%) vs. 22 out of 40 patients (55%) in the unit B (P=0.04). CONCLUSION: In our study, adding a visual aid depicting the evolution of the condition of critically ill patients day by day to classic oral information allowed the family to have an estimate of the prognosis less discordant with the estimate of the physician.

Predictors of Intubation in Patients With Acute Hypoxemic Respiratory Failure Treated With a Noninvasive Oxygenation Strategy.

OBJECTIVES: In patients with acute hypoxemic respiratory failure, noninvasive ventilation and high-flow nasal cannula oxygen are alternative strategies to conventional oxygen therapy. Endotracheal intubation is frequently needed in these patients with a risk of delay, and early predictors of failure may help clinicians to decide early. We aimed to identify factors associated with intubation in patients with acute hypoxemic respiratory failure treated with different noninvasive oxygenation techniques. DESIGN: Post hoc analysis of a randomized clinical trial. SETTING: Twenty-three ICUs. PATIENTS: Patients with a respiratory rate greater than 25 breaths/min and a PaO2/FIO2 ratio less than or equal to 300 mm Hg. INTERVENTION: Patients were treated with standard oxygen, high-flow nasal cannula oxygen, or noninvasive ventilation. MEASUREMENT AND MAIN RESULTS: Respiratory variables one hour after treatment initiation. Under standard oxygen, patients with a respiratory rate greater than or equal to 30 breaths/min were more likely to need intubation (odds ratio, 2.76; 95% CI, 1.13-6.75; p = 0.03). One hour after high-flow nasal cannula oxygen initiation, increased heart rate was the only factor associated with intubation. One hour after noninvasive ventilation initiation, a PaO2/FIO2 ratio less than or equal to 200 mm Hg and a tidal volume greater than 9 mL/kg of predicted body weight were independent predictors of intubation (adjusted odds ratio, 4.26; 95% CI, 1.62-11.16; p = 0.003 and adjusted odds ratio, 3.14; 95% CI, 1.22-8.06; p = 0.02, respectively). A tidal volume above 9 mL/kg during noninvasive ventilation remained independently associated with 90-day mortality. CONCLUSIONS: In patients with acute hypoxemic respiratory failure breathing spontaneously, the respiratory rate was a predictor of intubation under standard oxygen, but not under high-flow nasal cannula oxygen or noninvasive ventilation. A PaO2/FIO2 below 200 mm Hg and a high tidal volume greater than 9 mL/kg were the two strong predictors of intubation under noninvasive ventilation.

High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure.

BACKGROUND: Whether noninvasive ventilation should be administered in patients with acute hypoxemic respiratory failure is debated. Therapy with high-flow oxygen through a nasal cannula may offer an alternative in patients with hypoxemia. METHODS: We performed a multicenter, open-label trial in which we randomly assigned patients without hypercapnia who had acute hypoxemic respiratory failure and a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of 300 mm Hg or less to high-flow oxygen therapy, standard oxygen therapy delivered through a face mask, or noninvasive positive-pressure ventilation. The primary outcome was the proportion of patients intubated at day 28; secondary outcomes included all-cause mortality in the intensive care unit and at 90 days and the number of ventilator-free days at day 28. RESULTS: A total of 310 patients were included in the analyses. The intubation rate (primary outcome) was 38% (40 of 106 patients) in the high-flow-oxygen group, 47% (44 of 94) in the standard group, and 50% (55 of 110) in the noninvasive-ventilation group (P=0.18 for all comparisons). The number of ventilator-free days at day 28 was significantly higher in the high-flow-oxygen group (24±8 days, vs. 22±10 in the standard-oxygen group and 19±12 in the noninvasive-ventilation group; P=0.02 for all comparisons). The hazard ratio for death at 90 days was 2.01 (95% confidence interval [CI], 1.01 to 3.99) with standard oxygen versus high-flow oxygen (P=0.046) and 2.50 (95% CI, 1.31 to 4.78) with noninvasive ventilation versus high-flow oxygen (P=0.006). CONCLUSIONS: In patients with nonhypercapnic acute hypoxemic respiratory failure, treatment with high-flow oxygen, standard oxygen, or noninvasive ventilation did not result in significantly different intubation rates. There was a significant difference in favor of high-flow oxygen in 90-day mortality. (Funded by the Programme Hospitalier de Recherche Clinique Interrégional 2010 of the French Ministry of Health; FLORALI ClinicalTrials.gov number, NCT01320384.).

Therapeutic hypothermia after nonshockable cardiac arrest: the HYPERION multicenter, randomized, controlled, assessor-blinded, superiority trial.

BACKGROUND: Meta-analyses of nonrandomized studies have provided conflicting data on therapeutic hypothermia, or targeted temperature management (TTM), at 33°C in patients successfully resuscitated after nonshockable cardiac arrest. Nevertheless, the latest recommendations issued by the International Liaison Committee on Resuscitation and by the European Resuscitation Council recommend therapeutic hypothermia. New data are available on the adverse effects of therapeutic hypothermia, notably infectious complications. The risk/benefit ratio of therapeutic hypothermia after nonshockable cardiac arrest is unclear. METHODS: HYPERION is a multicenter (22 French ICUs) trial with blinded outcome assessment in which 584 patients with successfully resuscitated nonshockable cardiac arrest are allocated at random to either TTM between 32.5 and 33.5°C (therapeutic hypothermia) or TTM between 36.5 and 37.5°C (therapeutic normothermia) for 24 hours. Both groups are managed with therapeutic normothermia for the next 24 hours. TTM is achieved using locally available equipment. The primary outcome is day-90 neurological status assessed by the Cerebral Performance Categories (CPC) Scale with dichotomization of the results (1 + 2 versus 3 + 4 + 5). The primary outcome is assessed by a blinded psychologist during a semi-structured telephone interview of the patient or next of kin. Secondary outcomes are day-90 mortality, hospital mortality, severe adverse events, infections, and neurocognitive performance. The planned sample size of 584 patients will enable us to detect a 9% absolute difference in day-90 neurological status with 80% power, assuming a 14% event rate in the control group and a two-sided Type 1 error rate of 4.9%. Two interim analyses will be performed, after inclusion of 200 and 400 patients, respectively. DISCUSSION: The HYPERION trial is a multicenter, randomized, controlled, assessor-blinded, superiority trial that may provide an answer to an issue of everyday relevance, namely, whether TTM is beneficial in comatose patients resuscitated after nonshockable cardiac arrest. Furthermore, it will provide new data on the tolerance and adverse events (especially infectious complications) of TTM at 32.5-33.5°C. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01994772 .