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.
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.
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.
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.).
Abstract
Defining the hemodynamic response to volume therapy is integral to managing critically ill patients with acute circulatory failure, especially in the absence of cardiac index (CI) ...measurement. This study aimed at investigating whether changes in central venous-to-arterial CO
2
difference (Δ-ΔPCO
2
) and central venous oxygen saturation (ΔScvO
2
) induced by volume expansion (VE) are reliable parameters to define fluid responsiveness in sedated and mechanically ventilated septic patients. We prospectively studied 49 critically ill septic patients in whom VE was indicated because of circulatory failure and clinical indices. CI, ΔPCO
2
, ScvO
2
, and oxygen consumption (VO
2
) were measured before and after VE. Responders were defined as patients with a > 10% increase in CI (transpulmonary thermodilution) after VE. We calculated areas under the receiver operating characteristic curves (AUCs) for Δ-ΔPCO
2
, ΔScvO
2
, and changes in CI (ΔCI) after VE in the whole population and in the subgroup of patients with an increase in VO
2
(ΔVO
2
) ≤ 10% after VE (oxygen-supply independency). Twenty-five patients were fluid responders. In the whole population, Δ-ΔPCO
2
and ΔScvO
2
were significantly correlated with ΔCI after VE (r = − 0.30,
p
= 0.03 and r = 0.42,
p
= 0.003, respectively). The AUCs for Δ-ΔPCO
2
and ΔScvO
2
to define fluid responsiveness (increase in CI > 10% after VE) were 0.76 (
p
< 0.001) and 0.68 (
p
= 0.02), respectively. In patients with ΔVO
2
≤ 10% (n = 36) after VE, the correlation between ΔScvO
2
and ΔCI was 0.62 (
p
< 0.001), and between Δ-ΔPCO
2
and ΔCI was − 0.47 (
p
= 0.004). The AUCs for Δ-ΔPCO
2
and ΔScvO
2
were 0.83 (
p
< 0.001) and 0.73 (
p
= 0.006), respectively. In these patients, Δ-ΔPCO
2
≤ -37.5% after VE allowed the categorization between responders and non-responders with a positive predictive value of 100% and a negative predictive value of 60%. In sedated and mechanically ventilated septic patients with no signs of tissue hypoxia (oxygen-supply independency), Δ-ΔPCO
2
is a reliable parameter to define fluid responsiveness.
There have been few studies on the limitation of Life Supporting Care (LSC) and Withdrawal of LSC in Intermediate Care Units (IMCUs). We report the prevalence of LSC limited patients in a ...medico-surgical IMCU over a six-month period, examining the description, outcomes, and patterns of LSC Limitations and Withdrawal of LSC.
Single center, retrospective observational study in an IMCU of a 500-bed general hospital.
Our study of 404 patients, reported 79 (19.5%, 95%CI: 16.0-23.7%) being admitted with LSC limitations in the IMCU. This group of LSC limited patients presented with higher chronic and acute severity scores. The most common admission diagnosis of LSC limited patients was acute respiratory failure (51%). Non-invasive ventilation (NIV) was frequently used within this population (39%). Hospital mortality for LSC limited patients was high (53%) and associated with age (OR = 1.07, 95%CI: 1.01-1.13)), SOFA score (OR 1.29, 95%CI: 1.01-1.64), and hypoxemic respiratory failure (OR 7.2, 95%CI: 1.27-40.9). Withdrawal of LSC occurred in 19.5% of cases, often accompanied with terminal sedation with or without NIV removal (43.8%).
Patients with limitation of LSC are frequently admitted into IMCU. Hospital mortality rate was high and associated with age, acute organ failures, and hypoxemic respiratory failure. Life support withdrawal includes palliative sedation with or without NIV discontinuation.
To evaluate the extent to which sitting position and applied positive end-expiratory pressure improve respiratory mechanics of severely obese patients under mechanical ventilation.
Prospective cohort ...study.
A 15-bed ICU of a tertiary hospital.
Fifteen consecutive critically ill patients with a body mass index (the weight in kilograms divided by the square of the height in meters) above 35 were compared to 15 controls with body mass index less than 30.
Respiratory mechanics was first assessed in the supine position, at zero end-expiratory pressure, and then at positive end-expiratory pressure set at the level of auto-positive endexpiratory pressure. Second, all measures were repeated in the sitting position.
Assessment of respiratory mechanics included plateau pressure, auto-positive end-expiratory pressure, and flow-limited volume during manual compression of the abdomen, expressed as percentage of tidal volume to evaluate expiratory flow limitation. In supine position at zero end-expiratory pressure, all critically ill obese patients demonstrated expiratory flow limitation (flow-limited volume, 59.4% 51.3-81.4% vs 0% 0-0% in controls; p < 0.0001) and greater auto-positive end-expiratory pressure (10 5-12.5 vs 0.7 0.4-1.25 cm H2O in controls; p < 0.0001). Applied positive end-expiratory pressure reverses expiratory flow limitation (flow-limited volume, 0% 0-21% vs 59.4% 51-81.4% at zero end-expiratory pressure; p < 0.001) in almost all the obese patients, without increasing plateau pressure (24 19-25 vs 22 18-24 cm H2O at zero end-expiratory pressure; p = 0.94). Sitting position not only reverses partially or completely expiratory flow limitation at zero end-expiratory pressure (flow-limited volume, 0% 0-58% vs 59.4% 51-81.4% in supine obese patients; p < 0.001) but also results in a significant drop in auto-positive end-expiratory pressure (1.2 0.6-4 vs 10 5-12.5 cm H2O in supine obese patients; p < 0.001) and plateau pressure (15.6 14-17 vs 22 18-24 cm H2O in supine obese patients; p < 0.001).
In critically ill obese patients under mechanical ventilation, sitting position constantly and significantly relieved expiratory flow limitation and auto-positive end-expiratory pressure resulting in a dramatic drop in alveolar pressures. Combining sitting position and applied positive end-expiratory pressure provides the best strategy.
Acute respiratory failure (ARF) is a common life-threatening complication in morbidly obese patients with obesity hypoventilation syndrome (OHS). We aimed to identify the determinants of noninvasive ...ventilation (NIV) success or failure for this indication.
We prospectively included 76 consecutive patients with BMI>40 kg/m2 diagnosed with OHS and treated by NIV for ARF in a 15-bed ICU of a tertiary hospital.
NIV failed to reverse ARF in only 13 patients. Factors associated with NIV failure included pneumonia (n = 12/13, 92% vs n = 9/63, 14%; p<0.0001), high SOFA (10 vs 5; p<0.0001) and SAPS2 score (63 vs 39; p<0.0001) at admission. These patients often experienced poor outcome despite early resort to endotracheal intubation (in-hospital mortality, 92.3% vs 17.5%; p<0.001). The only factor significantly associated with successful response to NIV was idiopathic decompensation of OHS (n = 30, 48% vs n = 0, 0%; p = 0.001). In the NIV success group (n = 63), 33 patients (53%) experienced a delayed response to NIV (with persistent hypercapnic acidosis during the first 6 hours).
Multiple organ failure and pneumonia were the main factors associated with NIV failure and death in morbidly obese patients in hypoxemic ARF. On the opposite, NIV was constantly successful and could be safely pushed further in case of severe hypercapnic acute respiratory decompensation of OHS.
Central venous oxygen saturation (ScvO2) is often used to help to guide resuscitation of critically ill patients. The standard gold technique for ScvO2 measurement is the co-oximetry ...(Co-oximetry_ScvO2), which is usually incorporated in most recent blood gas analyzers. However, in some hospitals, those machines are not available and only calculated ScvO2 (Calc_ScvO2) is provided. Therefore, we aimed to investigate the agreement between Co-oximetry_ScvO2 and Calc_ScvO2 in a general population of critically ill patients and septic shock patients.
A total of 100 patients with a central venous catheter were included in the study. One hundred central venous blood samples were collected and analyzed using the same point-of-care blood gas analyzer, which provides both the calculated and measured ScvO2 values. Bland and Altman plot, intra-class correlation coefficient (ICC), and Cohen's Kappa coefficient were used to assess the agreement between Co-oximetry_ScvO2 and Calc_ScvO2. Multiple linear regression analysis was performed to investigate the independent explanatory variables of the difference between Co-oximetry_ScvO2 and Calc_ScvO2.
In all population, Bland and Altman's analysis showed poor agreement (+4.5 -7.1, +16.1%) between the two techniques. The ICC was 0.754 (95% CI: 0.393-0.880), P< 0.001, and the Cohen's Kappa coefficient, after categorizing the two variables into two groups using a cutoff value of 70%, was 0.470 (P <0.001). In septic shock patients (49%), Bland and Altman's analysis also showed poor agreement (+5.6 -6.7 to 17.8%). The ICC was 0.720 95% CI: 0.222-0.881, and the Cohen's Kappa coefficient was 0.501 (P <0.001). Four independent variables (PcvO2, Co-oximetry_ScvO2, venous pH, and Hb) were found to be associated with the difference between the measured and calculated ScvO2 (adjusted R2 = 0.8, P<0.001), with PcvO2 being the main independent explanatory variable because of its highest absolute standardized coefficient. The area under the receiver operator characteristic curves (AUC) of PcvO2 to predict Co-oximetry_ScvO2 ≥ 70% was 0.911 95% CI: 0.837-0.959, in all patients, and 0.903 95% CI: 0.784-0.969, in septic shock patients. The best cutoff value was ≥ 36 mmHg (sensitivity, 88%; specificity, 83%), in all patients, and ≥ 35 mmHg (sensitivity, 94%; specificity, 71%) in septic shock patients.
The discrepancy between the measured and calculated ScvO2 is clinically not acceptable. We do not recommend the use of calculated ScvO2 to guide resuscitation in critically ill patients. In situations where the Co-oximetry technique is not available, relying on PcvO2 to predict the measured ScvO2 value above or below 70% could be an option.
Microaspiration of gastric and oropharyngeal secretions is the main mechanism of entry of bacteria into the lower respiratory tract in intubated critically ill patients. The aim of this study is to ...determine the impact of enteral nutrition, as compared with parenteral nutrition, on abundant microaspiration of gastric contents and oropharyngeal secretions.
Planned ancillary study of the randomized controlled multicenter NUTRIREA2 trial. Patients with shock receiving invasive mechanical ventilation were randomized to receive early enteral or parenteral nutrition. All tracheal aspirates were collected during the 48 h following randomization. Abundant microaspiration of gastric contents and oropharyngeal secretions was defined as the presence of significant levels of pepsin (> 200 ng/ml) and salivary amylase (> 1685 UI/ml) in > 30% of tracheal aspirates.
A total of 151 patients were included (78 and 73 patients in enteral and parenteral nutrition groups, respectively), and 1074 tracheal aspirates were quantitatively analyzed for pepsin and amylase. Although vomiting rate was significantly higher (31% vs 15%, p = 0.016), constipation rate was significantly lower (6% vs 21%, p = 0.010) in patients with enteral than in patients with parenteral nutrition. No significant difference was found regarding other patient characteristics. The percentage of patients with abundant microaspiration of gastric contents was significantly lower in enteral than in parenteral nutrition groups (14% vs 36%, p = 0.004; unadjusted OR 0.80 (95% CI 0.69, 0.93), adjusted OR 0.79 (0.76, 0.94)). The percentage of patients with abundant microaspiration of oropharyngeal secretions was significantly higher in enteral than in parenteral nutrition groups (74% vs 54%, p = 0.026; unadjusted OR 1.21 (95% CI 1.03, 1.44), adjusted OR 1.23 (1.01, 1.48)). No significant difference was found in percentage of patients with ventilator-associated pneumonia between enteral (8%) and parenteral (10%) nutrition groups (HR 0.78 (0.26, 2.28)).
Our results suggest that enteral and parenteral nutrition are associated with high rates of microaspiration, although oropharyngeal microaspiration was more common with enteral nutrition and gastric microaspiration was more common with parenteral nutrition.
ClinicalTrials.gov, NCT03411447 . Registered 18 July 2017. Retrospectively registered.
Abstract Background Critical-illness survivors may experience post-traumatic stress disorder (PTSD) and quality-of-life impairments. Resilience may protect against psychological trauma but has not ...been adequately studied after critical illness. We assessed resilience and its associations with PTSD and quality of life, and also identified factors associated with greater resilience. Methods This prospective, multicentre, study in patients recruited at 41 French ICUs was done in parallel with the NUTRIREA-3 trial in patients given mechanical ventilation and vasoactive amines for shock. Three months to one year after intensive-care-unit admission, survivors completed the Connor-Davidson Resilience Scale (CD-RISC-25), Impact of Event-Revised scale for PTSD symptoms (IES-R), SF-36 quality-of-life scale, Multidimensional Scale of Perceived Social Support (MSPSS), and Brief Illness Perception Questionnaire (B-IPQ). Results Of the 382 included patients, 203 (53.1%) had normal or high resilience (CD-RISC-25 ≥ 68). Of these resilient patients, 26 (12.8%) had moderate to severe PTSD symptoms (IES-R ≥ 24) vs. 45 (25.4%) patients with low resilience ( p = 0.002). Resilient patients had higher SF-36 scores. Factors independently associated with higher CD-RISC-25 scores were higher MSPSS score indicating stronger social support (OR, 1.027; 95%CI 1.008–1.047; p = 0.005) and lower B-IPQ scores indicating a more threatening perception of the illness (OR, 0.973; 95%CI 0.950–0.996; p = 0.02). Conclusions Resilient patients had a lower prevalence of PTSD symptoms and higher quality of life scores, compared to patients with low resilience. Higher scores for social support and illness perception were independently associated with greater resilience. Thus, our findings suggest that interventions to strengthen social support and improve illness perception may help to improve resilience. Such interventions should be evaluated in trials with PTSD mitigation and quality-of-life improvement as the target outcomes.
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.
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