To the Editor: We report the neurologic features in an observational series of 58 of 64 consecutive patients admitted to the hospital because of acute respiratory distress syndrome (ARDS) due to Covid-19. The patients received similar evaluations by intensivists in two intensive care units (ICUs) in Strasbourg, France, between March 3 and April 3, 2020.Six patients were excluded because of paralytic neuromuscular blockade when neurologic data were collected or because they had died without a neurologic examination having been performed. In all 58 patients, reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of nasopharyngeal samples were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The median age of the patients was 63 years, and the median Simplified Acute Physiology Score II at the time of neurologic examination was 52 (interquartile range, 37 to 65, on a scale ranging from 0 to 163, with higher scores indicating greater severity of illness). Seven patients had had previous neurologic disorders, including transient ischemic attack, partial epilepsy, and mild cognitive impairment.The neurologic findings were recorded in 8 of the 58 patients (14%) on admission to the ICU (before treatment) and in 39 patients (67%) when sedation and a neuromuscular blocker were withheld. Agitation was present in 40 patients (69%) when neuromuscular blockade was discontinued (Table 1). A total of 26 of 40 patients were noted to have confusion according to the Confusion Assessment Method for the ICU; those patients could be evaluated when they were responsive (i.e., they had a score of −1 to 1 on the Richmond Agitation and Sedation Scale, on a scale of −5 [unresponsive] to +4 [combative]). Diffuse corticospinal tract signs with enhanced tendon reflexes, ankle clonus, and bilateral extensor plantar reflexes were present in 39 patients (67%). Of the patients who had been discharged at the time of this writing, 15 of 45 (33%) had had a dysexecutive syndrome consisting of inattention, disorientation, or poorly organized movements in response to command.

Intensive Care and Sepsis (CRICS) Group IMPORTANCE In the intensive care unit (ICU), orotracheal intubation can be associated with increased risk of complications because the patient may be acutely unstable, requiring prompt intervention, often by a practitioner with nonexpert skills. Video laryngoscopy may decrease this risk by improving glottis visualization. OBJECTIVE To determine whether video laryngoscopy increases the frequency of successful first-pass orotracheal intubation compared with direct laryngoscopy in ICU patients.DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial of 371 adults requiring intubation while being treated at 7 ICUs in France between May 2015 and January 2016; there was 28 days of follow-up.INTERVENTIONS Intubation using a video laryngoscope (n = 186) or direct laryngoscopy (n = 185). All patients received general anesthesia. MAIN OUTCOMES AND MEASURESThe primary outcome was the proportion of patients with successful first-pass intubation. The secondary outcomes included time to successful intubation and mild to moderate and severe life-threatening complications. RESULTS Among 371 randomized patients (mean [SD] age, 62.8 [15.8] years; 136 [36.7%] women), 371 completed the trial. The proportion of patients with successful first-pass intubation did not differ significantly between the video laryngoscopy and direct laryngoscopy groups (67.7% vs 70.3%; absolute difference, −2.5% [95% CI, −11.9% to 6.9%]; P = .60). The proportion of first-attempt intubations performed by nonexperts (primarily residents, n = 290) did not differ between the groups (84.4% with video laryngoscopy vs 83.2% with direct laryngoscopy; absolute difference 1.2% [95% CI, −6.3% to 8.6%]; P = .76). The median time to successful intubation was 3 minutes (range, 2 to 4 minutes) for both video laryngoscopy and direct laryngoscopy (absolute difference, 0 [95% CI, 0 to 0]; P = .95). Video laryngoscopy was not associated with life-threatening complications (24/180 [13.3%] vs 17/179 [9.5%] for direct laryngoscopy; absolute difference, 3.8% [95% CI, −2.7% to 10.4%]; P = .25). In post hoc analysis, video laryngoscopy was associated with severe life-threatening complications (17/179 [9.5%] vs 5/179 [2.8%] for direct laryngoscopy; absolute difference, 6.7% [95% CI, 1.8% to 11.6%]; P = .01) but not with mild to moderate life-threatening complications (10/181 [5.4%] vs 14/181 [7.7%]; absolute difference, −2.3% [95% CI, −7.4% to 2.8%]; P = .37).CONCLUSIONS AND RELEVANCE Among patients in the ICU requiring intubation, video laryngoscopy compared with direct laryngoscopy did not improve first-pass orotracheal intubation rates and was associated with higher rates of severe life-threatening complications. Further studies are needed to assess the comparative effectiveness of these 2 strategies in different clinical settings and among operators with diverse skill levels.

Clinicaltrials.gov Identifier NCT01449331.

IMPORTANCE Sepsis-associated acute kidney injury (AKI) adversely affects long-term kidney outcomes and survival. Administration of the detoxifying enzyme alkaline phosphatase may improve kidney function and survival. OBJECTIVE To determine the optimal therapeutic dose, effect on kidney function, and adverse effects of a human recombinant alkaline phosphatase in patients who are critically ill with sepsis-associated AKI. DESIGN, SETTING, AND PARTICIPANTS The STOP-AKI trial was an international (53 recruiting sites), randomized, double-blind, placebo-controlled, dose-finding, adaptive phase 2a/2b study in 301 adult patients admitted to the intensive care unit with a diagnosis of sepsis and AKI. Patients were enrolled between December 2014 and May 2017, and follow-up was conducted for 90 days. The final date of follow-up was August 14, 2017. INTERVENTIONS In the intention-to-treat analysis, in part 1 of the trial, patients were randomized to receive recombinant alkaline phosphatase in a dosage of 0.4 mg/kg (n = 31), 0.8 mg/kg (n = 32), or 1.6 mg/kg (n = 29) or placebo (n = 30), once daily for 3 days, to establish the optimal dose. The optimal dose was identified as 1.6 mg/kg based on modeling approaches and adverse events. In part 2, 1.6 mg/kg (n = 82) was compared with placebo (n = 86). MAIN OUTCOMES AND MEASURES The primary end point was the time-corrected area under the curve of the endogenous creatinine clearance for days 1 through 7, divided by 7 to provide a mean daily creatinine clearance (AUC 1-7 ECC). Incidence of fatal and nonfatal (serious) adverse events ([S]AEs) was also determined. RESULTS Overall, 301 patients were enrolled (men, 70.7%; median age, 67 years [interquartile range {IQR}, 59-73]). From day 1 to day 7, median ECC increased from 26.0 mL/min (IQR, 8.8 to 59.5) to 65.4 mL/min (IQR, 26.7 to 115.4) in the recombinant alkaline phosphatase 1.6-mg/kg group vs from 35.9 mL/min (IQR, 12.2 to 82.9) to 61.9 mL/min (IQR, 22.7 to 115.2) in the placebo group (absolute difference, 9.5 mL/min [95% CI, −23.9 to 25.5]; P = .47). Fatal adverse events occurred in 26.3% of patients in the 0.4-mg/kg recombinant alkaline phosphatase group; 17.1% in the 0.8-mg/kg group, 17.4% in the 1.6-mg/kg group, and 29.5% in the placebo group. Rates of nonfatal SAEs were 21.0% for the 0.4-mg/kg recombinant alkaline phosphatase group, 14.3% for the 0.8-mg/kg group, 25.7% for the 1.6-mg/kg group, and 20.5% for the placebo group. CONCLUSIONS AND RELEVANCE Among patients who were critically ill with sepsis-associated acute kidney injury, human recombinant alkaline phosphatase compared with placebo did not significantly improve short-term kidney function. Further research is necessary to assess other clinical outcomes.