Critically ill severe hypothyroidism: a retrospective multicenter cohort study.

BACKGROUND: Severe hypothyroidism (SH) is a rare but life-threatening endocrine emergency. Only a few data are available on its management and outcomes of the most severe forms requiring ICU admission. We aimed to describe the clinical manifestations, management, and in-ICU and 6-month survival rates of these patients. METHODS: We conducted a retrospective, multicenter study over 18 years in 32 French ICUs. The local medical records of patients from each participating ICU were screened using the International Classification of Disease 10th revision. Inclusion criteria were the presence of biological hypothyroidism associated with at least one cardinal sign among alteration of consciousness, hypothermia and circulatory failure, and at least one SH-related organ failure. RESULTS: Eighty-two patients were included in the study. Thyroiditis and thyroidectomy represented the main SH etiologies (29% and 19%, respectively), while hypothyroidism was unknown in 44 patients (54%) before ICU admission. The most frequent SH triggers were levothyroxine discontinuation (28%), sepsis (15%), and amiodarone-related hypothyroidism (11%). Clinical presentations included hypothermia (66%), hemodynamic failure (57%), and coma (52%). In-ICU and 6-month mortality rates were 26% and 39%, respectively. Multivariable analyses retained age > 70 years [odds ratio OR 6.01 (1.75-24.1)] Sequential Organ-Failure Assessment score cardiovascular component ≥ 2 [OR 11.1 (2.47-84.2)] and ventilation component ≥ 2 [OR 4.52 (1.27-18.6)] as being independently associated with in-ICU mortality. CONCLUSIONS: SH is a rare life-threatening emergency with various clinical presentations. Hemodynamic and respiratory failures are strongly associated with worse outcomes. The very high mortality prompts early diagnosis and rapid levothyroxine administration with close cardiac and hemodynamic monitoring.

Respective Impact of Day and Night Bed Baths on Critical Care Patients.

BACKGROUND: Despite data supporting the reduction of interactions with patients during nighttime, bed bathing is sometimes performed within this period in sedated patients unable to manage their own hygiene care. OBJECTIVES: To compare patient physiologic variables and adverse effect incidence between night and day bed baths. METHODS: This was a single-center prospective observational study in a 12-bed intensive care unit during 2 months. Night period was defined to run from 10 pm to 6 am. Night bed baths were provided to sedated ventilated patients whatever their sedation, if their Richmond Agitation Sedation Scale score was -2 or deeper. Bed bath-induced changes in physiological variables, treatments, and related unscheduled events were registered during both night and day bed baths. RESULTS: Twenty-one patients (aged 62.9 [52.5-73.2] years, 14 male patients) were included. We registered 97 night bed baths and 95 day bed baths. Heart rate increased only after day bed baths (85 beats/min [bpm] [69-97 bpm] vs 88 bpm [73-98 bpm], P = .02). Increase in Richmond Agitation Sedation Scale score occurred, respectively, during 13 (13.4%) and 8 (8.4%) night and day bed baths, without significant differences. Body temperature significantly decreased during both night and day bed baths (respectively, 37°C [36.6°C-37.4°C] vs 36.6°C [36.2°C-37.2°C], P < .0001; and 36.9°C [36.5°C-37.2°C] vs 36.7°C [36.2°C-37.2°C], P = .0006). Overall, unscheduled events, whether physiologic changes, pain, or calling a physician in rescue occurred in 97 procedures (50.5%), irrespective of their timing (night vs day, respectively 53% [54.6%] vs 44% [46.3%], P = .31). DISCUSSION: Although unscheduled events occurred in half of bed baths, differences evidenced between nighttime and daytime bed baths were scarce. The appropriateness of nighttime bed bathing remains questionable.

Handgrip strength to predict extubation outcome: a prospective multicenter trial.

BACKGROUND: ICU-acquired weakness (ICUAW) has been shown to be associated with prolonged duration of mechanical ventilation and extubation failure. It is usually assessed through Medical Research Council (MRC) score, a time-consuming score performed by physiotherapists. Handgrip strength (HG) can be monitored very easily at the bedside. It has been shown to be a reproducible and reliable marker of global muscular strength in critical care patients. We sought to test if muscular weakness, as assessed by handgrip strength, was associated with extubation outcome. METHODS: Prospective multicenter trial over an 18 months period in six mixed ICUs. Adults receiving mechanical ventilation for at least 48 h were eligible. Just before weaning trial, HG, Maximal Inspiratory Pressure (MIP), Peak Cough Expiratory Flow (PCEF) and Medical Research Council (MRC) score were registered. The attending physicians were unaware of the tests results and weaning procedures were conducted according to guidelines. Occurrence of unscheduled reintubation, non-invasive ventilation (NIV) or high-flow nasal continuous oxygen (HFNC) because of respiratory failure within 7 days after extubation defined extubation failure. The main outcome was the link between HG and extubation outcome. RESULTS: 233 patients were included. Extubation failure occurred in 51 (22.5%) patients, 39 (17.2%) required reintubation. Handgrip strength was 12 [6-20] kg and 12 [8-20] kg, respectively, in extubation success and failure (p = 0.85). There was no association between extubation outcome and MRC score, MIP or PCEF. Handgrip strength was well correlated with MRC score (r = 0.718, p < 0.0001). ICU and hospital length of stay were significantly higher in the subset of patients harboring muscular weakness as defined by handgrip performed at the first weaning trial (respectively, 15 [10-25] days vs. 11 [7-17] days, p = 0.001 and 34 [19-66] days vs. 22 [15-43] days, p = 0.002). CONCLUSION: No association was found between handgrip strength and extubation outcome. Whether this was explained by the appropriateness of the tool in this specific setting, or by the precise impact of ICUAW on extubation outcome deserves to be further evaluated. Trial registration Clinical Trials; NCT02946502, 10/27/2016, URL: https://clinicaltrials.gov/ct2/results?cond=&term=gripwean&cntry=&state=&city=&dist=.

Changes in pulse pressure variation to assess preload responsiveness in mechanically ventilated patients with spontaneous breathing activity: an observational study.

BACKGROUND: Pulse pressure variation (PPV) is not reliable in predicting preload responsiveness in patients receiving mechanical with spontaneous breathing (SB) activity. We hypothesised that an increase in PPV after a tidal volume (VT) challenge (TVC) or a decrease in PPV during passive leg raising (PLR) can predict preload responsiveness in such cases. METHODS: This prospective observational study was performed in two ICUs and included patients receiving mechanical ventilation with SB, for whom the treating physician decided to test preload responsiveness. Transthoracic echocardiography was used to measure the velocity-time integral (VTI) of the left ventricular outflow tract. Patients exhibiting an increase in VTI ≥12% during PLR were defined as PLR+ patients (or preload responders). Then, a TVC was performed by increasing VT by 2 ml kg-1 predicted body weight (PBW) for 1 min. PPV was recorded at each step. RESULTS: Fifty-four patients (Simplified Acute Physiology Score II: 60 (25) ventilated with a VT of 6.5 (0.8) ml kg-1 PBW, were included. Twenty-two patients were PLR+. The absolute decrease in PPV during PLR and the absolute increase in PPV during TVC discriminated between PLR+ and PLR- patients with area under the receiver operating characteristic (AUROC) curve of 0.78 and 0.73, respectively, and cut-off values of -1% and +2%, respectively. Those AUROC curve values were similar but were significantly different from that of baseline PPV (0.61). CONCLUSION: In patients undergoing mechanical ventilation with SB activity, PPV does not predict preload responsiveness. However, the decrease in PPV during PLR and the increase in PPV during a TVC help discriminate preload responders from non-responders with moderate accuracy. CLINICAL TRIAL REGISTRATION: NCT04369027 (ClinicalTrials.gov).

Are bedside colonoscopies performed in intensive care unit really useful?

PURPOSE: Effectiveness of bedside Colonoscopies in Intensive Care Unit (CICU) might be limited by the poor quality of colonic preparation, and their feasibility. We sought to describe the indications and the profitability of CICU. METHODS: Retrospective, bicenter observational study (2004-2015) in unselected critically ill patients. We questioned the clinical profitability of CICU, according to its indications and preparation. RESULTS: One hundred and eleven CICU were performed in 84 patients (sex ratio 1.4, 49 M/35F; age 72.9 years [61.7-84.7]), for lower gastro-intestinal bleeding in 67 patients (LGIB, 60.3%) and for other causes in 44 (39.6%). The profitability was more frequent when CICU was performed for another reason than LGIB (75% vs 28.3%; p < 0.0001). Preparation was good in 47 procedures (42.3%) and allowed 33 complete CICU (29.7%). Fifty-six CICU (50.4%) were performed as a 2nd investigation after a contrast enhanced computed tomography. Three CICU were complicated by 3 hemodynamic and 2 respiratory failures, but none of them were fatal. CONCLUSIONS: CICU is clinically useful in half of cases, in the diagnostic and the therapeutic management of critically ill patients. Its profitability is close to scheduled colonoscopies and superior in non-lower gastro-intestinal bleeding indications.

Life Support Limitations in Mechanically Ventilated Stroke Patients.

OBJECTIVES: The determinants of decisions to limit life support (withholding or withdrawal) in ventilated stroke patients have been evaluated mainly for patients with intracranial hemorrhages. We aimed to evaluate the frequency of life support limitations in ventilated ischemic and hemorrhagic stroke patients compared with a nonbrain-injured population and to determine factors associated with such decisions. DESIGN: Multicenter prospective French observational study. SETTING: Fourteen ICUs of the French OutcomeRea network. PATIENTS: From 2005 to 2016, we included stroke patients and nonbrain-injured patients requiring invasive ventilation within 24 hours of ICU admission. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: We identified 373 stroke patients (ischemic, n = 167 [45%]; hemorrhagic, n = 206 [55%]) and 5,683 nonbrain-injured patients. Decisions to limit life support were taken in 41% of ischemic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.59 [95% CI, 2.78-4.65]) and in 33% of hemorrhagic stroke cases (vs nonbrain-injured patients, subdistribution hazard ratio, 3.9 [95% CI, 2.97-5.11]). Time from ICU admission to the first limitation was longer in ischemic than in hemorrhagic stroke (5 [3-9] vs 2 d [1-6] d; p < 0.01). Limitation of life support preceded ICU death in 70% of ischemic strokes and 45% of hemorrhagic strokes (p < 0.01). Life support limitations in ischemic stroke were increased by a vertebrobasilar location (vs anterior circulation, subdistribution hazard ratio, 1.61 [95% CI, 1.01-2.59]) and a prestroke modified Rankin score greater than 2 (2.38 [1.27-4.55]). In hemorrhagic stroke, an age greater than 70 years (2.29 [1.43-3.69]) and a Glasgow Coma Scale score less than 8 (2.15 [1.08-4.3]) were associated with an increased risk of limitation, whereas a higher nonneurologic admission Sequential Organ Failure Assessment score was associated with a reduced risk (per point, 0.89 [0.82-0.97]). CONCLUSIONS: In ventilated stroke patients, decisions to limit life support are more than three times more frequent than in nonbrain-injured patients, with different timing and associated risk factors between ischemic and hemorrhagic strokes.

Increase in Central Venous Pressure During Passive Leg Raising Cannot Detect Preload Unresponsiveness.

OBJECTIVE: By analogy with the classical central venous pressure rules to assess a fluid challenge, we hypothesized that an increase in central venous pressure greater than or equal to 5 cm H2O (i.e., 4 mm Hg) during passive leg raising can predict preload unresponsiveness diagnosed by the absence of increase in velocity-time integral of the left ventricular outflow tract greater than or equal to 10% during the test (negative passive leg raising test). DESIGN AND SETTINGS: Velocity-time integral was measured by transthoracic echocardiography. Central venous pressure and velocity-time integral were measured before and during passive leg raising. PATIENTS: Critically ill patients for whom the physician decided to test preload responsiveness by passive leg raising were prospectively included. MEASUREMENT AND MAIN RESULTS: Fifty-seven set of measurements were performed in 50 patients. Preload unresponsiveness (negative passive leg raising test) was observed in 32 cases. The changes in central venous pressure during passive leg raising did not differ between positive passive leg raising cases (positive passive leg raising test) and negative passive leg raising test cases (3 ± 2 vs 3 ± 2 mm Hg, respectively) and thus did not predict preload unresponsiveness (area under the receiver-operating characteristic curve of 0.59). An increase in central venous pressure greater than or equal to 4 mm Hg during passive leg raising was observed in 10 cases of positive passive leg raising test and in 11 cases of negative passive leg raising test. Taking an increase in central venous pressure greater than or equal to 3 or greater than or equal to 5 mm Hg rather than greater than or equal to 4 mm Hg during passive leg raising did not better allow one to identify negative passive leg raising test. CONCLUSIONS: Marked increase in central venous pressure during passive leg raising cannot identify negative passive leg raising test cases and thus preload unresponsiveness. Measurements of cardiac output (or its surrogates) during passive leg raising are, thus, mandatory to appropriately interpret this test.

One-year survival in acute stroke patients requiring mechanical ventilation: a multicenter cohort study.

BACKGROUND: Most prognostic studies in acute stroke patients requiring invasive mechanical ventilation are outdated and have limitations such as single-center retrospective designs. We aimed to study the association of ICU admission factors, including the reason for intubation, with 1-year survival of acute stroke patients requiring mechanical ventilation. METHODS: We conducted a secondary data use analysis of a prospective multicenter database (14 ICUs) between 1997 and 2016 on consecutive ICU stroke patients requiring mechanical ventilation at admission. We excluded patients with stroke of traumatic origin, subdural hematoma or cerebral venous thrombosis. The primary outcome was survival 1 year after ICU admission. Factors associated with the primary outcome were identified using a multivariable Cox model stratified on inclusion center. RESULTS: We identified 419 patients (age 68 [58-76] years, males 60%) with a Glasgow coma score (GCS) of 4 [3-8] at admission. Stroke subtypes were acute ischemic stroke (AIS, 46%), intracranial hemorrhage (ICH, 42%) and subarachnoid hemorrhage (SAH, 12%). At 1 year, 96 (23%) patients were alive. Factors independently associated with decreased 1-year survival were ICH and SAH stroke subtypes, a lower GCS score at admission, a higher non-neurological SOFA score. Conversely, patients receiving acute-phase therapy had improved 1-year survival. Intubation for acute respiratory failure or coma was associated with comparable survival hazard ratios, whereas intubation for seizure was not associated with a worse prognosis than for elective procedure. Survival did not improve over the study period, but patients included in the most recent period had more comorbidities and presented higher severity scores at admission. CONCLUSIONS: In acute stroke patients requiring mechanical ventilation, the reason for intubation and the opportunity to receive acute-phase stroke therapy were independently associated with 1-year survival. These variables could assist in the decision process regarding the initiation of mechanical ventilation in acute stroke patients.

Initial management of diabetic ketoacidosis and prognosis according to diabetes type: a French multicentre observational retrospective study.

BACKGROUND: Guidelines for the management of diabetic ketoacidosis (DKA) do not consider the type of underlying diabetes. We aimed to compare the occurrence of metabolic adverse events and the recovery time for DKA according to diabetes type. METHODS: Multicentre retrospective study conducted at five adult intermediate and intensive care units in Paris and its suburbs, France. All patients admitted for DKA between 2013 and 2014 were included. Patients were grouped and compared according to the underlying type of diabetes into three groups: type 1 diabetes, type 2 or secondary diabetes, and DKA as the first presentation of diabetes. Outcomes of interest were the rate of metabolic complications (hypoglycaemia or hypokalaemia) and the recovery time. RESULTS: Of 122 patients, 60 (49.2%) had type 1 diabetes, 28 (22.9%) had type 2 or secondary diabetes and 34 (27.9%) presented with DKA as the first presentation of diabetes (newly diagnosed diabetes). Despite having received lower insulin doses, hypoglycaemia was more frequent in patients with type 1 diabetes (76.9%) than in patients with type 2 or secondary diabetes (50.0%) and in patients with newly diagnosed diabetes (54.6%) (p = 0.026). In contrast, hypokalaemia was more frequent in the latter group (82.4%) than in patients with type 1 diabetes (57.6%) and type 2 or secondary diabetes (51.9%) (p = 0.022). The median recovery times were not significantly different between groups. CONCLUSIONS: Rates of metabolic complications associated with DKA treatment differ significantly according to underlying type of diabetes. Decreasing insulin dose may limit those complications. DKA treatment recommendations should take into account the type of diabetes.

Pneumonia in acute ischemic stroke patients requiring invasive ventilation: Impact on short and long-term outcomes.

OBJECTIVES: To describe the epidemiology and prognostic impact of pneumonia in acute ischemic stroke patients requiring invasive mechanical ventilation. METHODS: Retrospective analysis from a prospective multicenter cohort study of critically ill patients with acute ischemic stroke requiring invasive mechanical ventilation at admission. Impact of pneumonia was investigated using Cox regression for 1-year mortality, and competing risk survival models for ICU mortality censored at 30-days. RESULTS: We included 195 patients. Stroke was supratentorial in 62% and 64% of patients had a Glasgow coma scale score <8 on admission. Mortality at day-30 and 1 year were 56%, and 70%, respectively. Post-stroke pneumonia was identified in 78 (40%) patients, of which 46/78 (59%) episodes were present at ICU admission. Post-stroke pneumonia was associated with an increase in 1-year mortality (adjusted HR 1.49, 95%CI [1.01-2.20]). Post-stroke pneumonia was not associated with ICU mortality but was associated with a 1.6-fold increase in ICU length of stay (CSHR 0.62 [0.39-0.99], p = 0.06). CONCLUSIONS: In ischemic stroke patients requiring invasive ventilation, pneumonia occurred in 40% of cases and was associated with a 49% increase in 1-year mortality. Post-stroke pneumonia did not impact day-30 mortality but increased ICU length of stay.

Effect of Noninvasive Ventilation After Unplanned Extubation.

BACKGROUND: Our study set out to test the effect of noninvasive ventilation (NIV) performed after unplanned extubation. METHODS: Retrospective analysis of prospectively collected data in a university-affiliated mixed ICU of 12 beds during a 5-y period (January 2013 to December 2017). Unplanned extubation was defined as the occurrence of an unplanned removal of the endotracheal tube, whether deliberate or accidental. NIV after an unplanned extubation was not protocolized and was decided by the physician in charge on an individual basis. RESULTS: A total of 121 subjects (median [25th-75th percentile] age, 62.1 [43.3-73.6] y; median [25th-75th percentile] Simplified Acute Physiology Score II, 45 [36-54]) experienced 131 unplanned extubation episodes. Re-intubation was deemed necessary in 35 subjects (28.9%). NIV was used in 24 subjects (19.8%) (prophylactic NIV, n = 10; rescue NIV, n = 14). The re-intubation rates were 25.8%, 10%, and 64.3% in the no NIV, prophylactic, and rescue NIV subgroups, respectively. The median (25th-75th percentile) time to re-intubation was longer for subjects on NIV (9.1 [3.5-49.2] vs 0.46 [0.25-1] h, P = .001). The median (25th-75th percentile) ICU length of stay and duration of mechanical ventilation were longer in the subjects who underwent NIV (14.5 [7-24.5] vs 6 [3-14] d, respectively, P = .004; and 9 [3-22] vs 3 [1-7.3] d, respectively, P = .003). CONCLUSIONS: NIV after unplanned extubation had uncertain efficacy, especially when provided as rescue management of postextubation respiratory failure.

An Index Combining Respiratory Rate and Oxygenation to Predict Outcome of Nasal High-Flow Therapy.

Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives: To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/FiO2 to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods: This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results: Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/FiO2 had a greater weight than respiratory rate. Conclusions: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).

Constipation in critical care patients: both timing and duration matter.

OBJECTIVE: Most of the studies have defined constipation as a period without stool after ICU admission. We aimed to test the impact of both duration and timing of infrequent defecation in critical care patients. PATIENTS AND METHODS: We performed a prospective, bi-center, observational study. Patients were divided into three subgroups: 'not constipated', '3-5 days', and 'at least 6 days' (longest period without stool passage, respectively, shorter than 3 days, 3-5 days, and ≥6 days). Furthermore, 'early' constipated patients were defined as those for whom the longest time to stool passage occurred just after ICU admission, whereas for 'late' constipated patients the longest period without stool occurred later during ICU stay. RESULTS: A total of 182 patients were included: the mean age was 67.2 years (54.4-78.9 years), 80 were women, and simplified acute physiology score II was 42 (34-52). In all, 42 (23.1%), 82 (45.1%), and 58 (31.8%) belonged to the nonconstipated, 3-5 days, or greater than or equal to 6 days subgroup of patients, respectively. Time spent under mechanical ventilation and ICU length of stay was longer in the greater than or equal to 6 days subgroups as compared with both other subgroups. ICU stay was longer in the 3-5 days subgroup as compared with the not constipated patients. Furthermore, the late patients of the greater than or equal to 6 days subgroups exhibited worse survival as compared with all other patients. CONCLUSION: Both timing and duration of infrequent defecation seem to have an impact on critical care patient's outcome, and should therefore be included in the diagnostic criteria.

Loxapine to control agitation during weaning from mechanical ventilation.

BACKGROUND: Weaning from mechanical ventilation (MV) may be impeded by the occurrence of agitation. Loxapine has the ability to control agitation without affecting spontaneous ventilation. The aim of this study was to establish whether loxapine would reduce MV weaning duration in agitated patients. METHODS: We performed a multicentre, double-blind, placebo-controlled, parallel group, randomised trial. Patients who were potential candidates for weaning but exhibited agitation (Richmond Agitation-Sedation Scale score ≥ 2) after sedation withdrawal were randomly assigned to receive either loxapine or placebo. In case of severe agitation, conventional sedation was immediately resumed. The primary endpoint was the time between first administration of loxapine or placebo and successful extubation. RESULTS: The trial was discontinued after 102 patients were enrolled because of an insufficient inclusion rate. Median times to successful extubation were 3.2 days in the loxapine group and 5 days in the placebo group (relative risk 1.2, 95% CI 0.75-1.88, p = 0.45). During the first 24 h, sedation was more frequently resumed in the placebo group (44% vs 17%, p = 0.01). CONCLUSIONS: In this prematurely stopped trial, loxapine did not significantly shorten weaning from MV. However, loxapine reduced the need for resuming sedation. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01193816 . Registered on 26 August 2010.