Anemia is very common in aneurysmal subarachnoid hemorrhage (aSAH), with approximately half of the aSAH patient population developing moderate anemia during their hospital stay. The available ...evidence (both physiologic and clinical) generally supports an association of anemia with unfavorable outcomes. Although aSAH shares a number of common mechanisms of secondary insult with other forms of acute brain injury, aSAH also has specific features that make it unique: an early phase (in which early brain injury predominates) and a delayed phase (in which delayed cerebral ischemia and vasospasm predominate). The effects of both anemia and transfusion are potentially variable between these phases, which may have unique considerations and possibly different risk–benefit profiles. Data on transfusion in this population are almost exclusively limited to observational studies, which suffer from significant heterogeneity and risk of bias. Overall, the results are conflicting, with the balance of the studies suggesting that transfusion is associated with unfavorable outcomes. The transfusion targets that are well established in other critically ill populations should not be automatically applied to patients with aSAH because of the unique disease characteristics of this population and the limited representation of aSAH in the clinical trials that established these targets. There are two upcoming clinical trials evaluating transfusion in aSAH that should help clarify specific transfusion targets. Until then, it is reasonable to base transfusion decisions on the current guidelines and use an individualized approach incorporating physiologic and clinical data when available.
Clinicians' current practice patterns in the management of acute respiratory distress syndrome (ARDS) and refractory hypoxemia are not well described.
To describe mechanical ventilation strategies ...and treatment adjuncts for adults with ARDS, including refractory hypoxemia.
This was a prospective cohort study (March 2014-February 2015) of mechanically ventilated adults with moderate-to-severe ARDS requiring an Fi
of 0.50 or greater in 24 intensive care units.
We enrolled 664 patients: 222 (33%) with moderate and 442 (67%) with severe ARDS. On Study Day 1, mean Vt was 7.5 (SD = 2.1) ml/kg predicted body weight (n = 625); 80% (n = 501) received Vt greater than 6 ml/kg. Mean positive end-expiratory pressure (PEEP) was 10.5 (3.7) cm H
O (n = 653); 568 patients (87%) received PEEP less than 15 cm H
O. Treatment adjuncts were common (n = 440, 66%): neuromuscular blockers (n = 276, 42%), pulmonary vasodilators (n = 118, 18%), prone positioning (n = 67, 10%), extracorporeal life support (n = 29, 4%), and high-frequency oscillatory ventilation (n = 29, 4%). Refractory hypoxemia, defined as Pa
less than 60 mm Hg on Fi
of 1.0, occurred in 138 (21%) patients. At onset of refractory hypoxemia, mean Vt was 7.1 (SD = 2.0) ml/kg (n = 124); 95 patients (77%) received Vt greater than 6 ml/kg. Mean PEEP was 12.1 (SD = 4.4) cm H
O (n = 133); 99 patients (74%) received PEEP less than 15 cm H
O. Among patients with refractory hypoxemia, 91% received treatment adjuncts (126/138), with increased use of neuromuscular blockers (n = 87, 63%), pulmonary vasodilators (n = 57, 41%), and prone positioning (n = 32, 23%).
Patients with moderate-to-severe ARDS receive treatment adjuncts frequently, especially with refractory hypoxemia. Paradoxically, therapies with less evidence supporting their use (e.g., pulmonary vasodilators) were over-used, whereas those with more evidence (e.g., prone positioning, neuromuscular blockade) were under-used. Patients received higher Vts and lower PEEP than would be suggested by the evidence.
Abstract
Background
Nirmatrelvir/ritonavir has shown to reduce COVID-19 hospitalization and death before Omicron, but updated real-world evidence studies are needed. This study aimed to assess ...whether nirmatrelvir/ritonavir reduces the risk of COVID-19–associated hospitalization among high-risk outpatients.
Methods
A retrospective cohort study of outpatients with SARS-CoV-2 between March 15 and 15 October 2022, using data from the Quebec clinico-administrative databases. Outpatients treated with nirmatrelvir/ritonavir were compared with infected ones not receiving nirmatrelvir/ritonavir using propensity-score matching. Relative risk (RR) of COVID-19–associated hospitalization within 30 days was assessed using a Poisson regression.
Results
A total of 8402 treated outpatients were matched to controls. Regardless of vaccination status, nirmatrelvir/ritonavir treatment was associated with a 69% reduced RR of hospitalization (RR: .31; 95% CI: .28; .36; number needed to treat NNT = 13). The effect was more pronounced in outpatients with incomplete primary vaccination (RR: .04; 95% CI: .03; .06; NNT = 8), while no benefit was found in those with a complete primary vaccination (RR: .93; 95% CI: .78; 1.08). Subgroups analysis among high-risk outpatients with a complete primary vaccination showed that nirmatrelvir/ritonavir treatment was associated with a significant decrease in the RR of hospitalization in severely immunocompromised outpatients (RR: .66; 95% CI: .50; .89; NNT = 16) and in high-risk outpatients aged ≥70 years (RR: .50; 95% CI: .34; .74; NNT = 10) when the last dose of the vaccine was received at least 6 months ago.
Conclusions
Nirmatrelvir/ritonavir reduces the risk of COVID-19–associated hospitalization among incompletely vaccinated high-risk outpatients and among some subgroups of completely vaccinated high-risk outpatients.
Nirmatrelvir/ritonavir treatment was associated with a significant reduced risk of hospitalization among incompletely primary vaccinated high-risk outpatients, but no benefit was found for completely vaccinated high-risk outpatients who received their last dose within 6 months, except among immunocompromised outpatients.
Glutamine is thought to have beneficial effects on the metabolic and stress response to severe injury. Clinical trials involving patients with burns and other critically ill patients have shown ...conflicting results regarding the benefits and risks of glutamine supplementation.
In a double-blind, randomized, placebo-controlled trial, we assigned patients with deep second- or third-degree burns (affecting ≥10% to ≥20% of total body-surface area, depending on age) within 72 hours after hospital admission to receive 0.5 g per kilogram of body weight per day of enterally delivered glutamine or placebo. Trial agents were given every 4 hours through a feeding tube or three or four times a day by mouth until 7 days after the last skin grafting procedure, discharge from the acute care unit, or 3 months after admission, whichever came first. The primary outcome was the time to discharge alive from the hospital, with data censored at 90 days. We calculated subdistribution hazard ratios for discharge alive, which took into account death as a competing risk.
A total of 1209 patients with severe burns (mean burn size, 33% of total body-surface area) underwent randomization, and 1200 were included in the analysis (596 patients in the glutamine group and 604 in the placebo group). The median time to discharge alive from the hospital was 40 days (interquartile range, 24 to 87) in the glutamine group and 38 days (interquartile range, 22 to 75) in the placebo group (subdistribution hazard ratio for discharge alive, 0.91; 95% confidence interval CI, 0.80 to 1.04; P = 0.17). Mortality at 6 months was 17.2% in the glutamine group and 16.2% in the placebo group (hazard ratio for death, 1.06; 95% CI, 0.80 to 1.41). No substantial between-group differences in serious adverse events were observed.
In patients with severe burns, supplemental glutamine did not reduce the time to discharge alive from the hospital. (Funded by the U.S. Department of Defense and the Canadian Institutes of Health Research; RE-ENERGIZE ClinicalTrials.gov number, NCT00985205.).
There is significant heterogeneity in the reporting of outcome measures in aneurysmal subarachnoid hemorrhage (aSAH) research. The modified Rankin scale (mRS) is the most commonly reported functional ...outcome measure. The mRS focuses on physical disability; however, many aSAH survivors experience sequalae in other domains, and the mRS may therefore not capture outcomes important to aSAH survivors. The objective of this study was to assess the clinical relevance of the mRS as a research outcome measure to people with lived aSAH experience.
We conducted an international cross-sectional survey of 355 aSAH survivors, family members, and caregivers to evaluate patient-perceived outcomes in relation to the mRS. The mRS was assessed using a previously validated web-based tool.
Response rate was 60%; respondents from 7 continents were composed of 86% aSAH survivors and 14% family members/caregivers. Agreement between self-assessed outcome and the mRS was poor (Kappa 0.26 CI 0.14-0.39). Of the 172 respondents who self-assessed as having had a good aSAH outcome, 122 (71%) had a score of 0-2 on the mRS. Approximately 19% of respondents with a good outcome, based on a measured mRS score of 0-2, self-assessed as having had a poor aSAH outcome. When the mRS score was dichotomized as 0-3 corresponding to a good outcome, agreement between the score and self-assessed outcome remained poor with a Kappa score of 0.40 (CI 0.20-0.60). Approximately 30% of respondents believed that the mRS should not be used as an outcome measure in future aSAH trials.
The findings suggest that there is poor agreement between aSAH survivors' self-assessed outcome, their actual mRS score, and the dichotomization of the mRS score into good/poor outcomes. Patient-centered and patient-informed outcome measurement tools are needed to guide the aSAH research agenda.
Abstract Background Liver resection is associated with a high proportion of red blood cell transfusions. There is a proposed association between perioperative transfusions and increased risk of ...complications and tumor recurrence. This study reviews the evidence of this association in the literature. Methods The Medline, EMBASE, and Cochrane databases were searched for clinical trials or observational studies of patients undergoing liver resection that compared patients who did and did not receive a perioperative red blood cell transfusion. Outcomes were mortality, complications, and cancer survival. Results Twenty-two studies involving 6832 patients were included. All studies were retrospective, with no clinical trials. No studies were scored as low risk of bias. The overall proportion of patients transfused was 38.3%. After multivariate analysis, 1 of 5 studies demonstrated an association between transfusion and increased mortality; 5 of 6 demonstrated an association between transfusion and increased complications; and 10 of 18 demonstrated an association between transfusion and decreased cancer survival. Conclusion This review supports the evidence linking perioperative blood transfusions to negative outcomes. The most convincing association was with post-operative complications, some association with long-term cancer outcomes, and no convincing association with mortality. These findings support the initiation, and further study, of restrictive transfusion protocols.
Introduction
Various strategies have been proposed for postoperative pain control. Among those, intravenous lidocaine infusion (IVLI) has gained in interest. However, its clinical benefit remains ...unclear. This systematic review is an evaluation of the analgesic efficacy and safety of IVLI during general anesthesia.
Methods
A systematic search was performed using MEDLINE, EMBASE, Cochrane, and SCOPUS databases, likewise, grey literature. The review included all randomized controlled trials that used a placebo or any comparator and evaluated IVLI during general anesthesia for any type of surgery. Primary outcomes were pain control and opioid requirement. Secondary outcomes were mortality, length of stay, ileus recovery time, nausea/vomiting, and adverse events. Random effects models were used and heterogeneity was assessed using the I
2
index.
Results
From 5,472 citations retrieved, 29 studies involving a total of 1,754 patients met eligibility. At six hours postoperatively, intravenous lidocaine infusion reduced pain at rest (weighted mean difference WMD −8.70, 95% confidence intervals CI −16.19 to −1.21), during cough (WMD −11.19, 95% CI −17.73 to −4.65), and during movement (WMD −9.56, 95% CI −17.31 to −1.80). Intravenous lidocaine infusion also reduced opioid requirement (morphine) (WMD −8.44 mg, 95% CI −11.32 to −5.56), time to first flatus (WMD −7.62 hr, 95% CI −10.78 to −4.45), time to first feces (WMD −10.71 hr, 95% CI −16.14 to −5.28), nausea/vomiting (risk ratios = 0.71, 95% CI 0.57-0.90), and hospital length of stay (WMD −0.17 days, 95% CI −0.41 to 0.07). Abdominal surgery was strongly associated with benefit. For the 12 studies that systematically screened adverse events, the incidence of cardiac and neurologic adverse events was comparable. Eight studies observed toxic plasma levels.
Discussion
Perioperative IVLI reduced postoperative pain and opioid requirement, as well as ileus recovery time, hospital length of stay, and nausea/vomiting. Intravenous lidocaine infusion was effective mainly in abdominal surgery populations. Considering that toxic levels were detected and that adverse events were not systematically screened for in most studies, dose and safety of IVLI should be established before recommending its use.
With the recognition of early coagulopathy, trauma resuscitation has shifted toward liberal platelet transfusions. The overall benefit of this strategy remains controversial. Our objective was to ...compare the effects of a liberal use of platelet (higher platelet:RBC ratios) with a conservative approach (lower ratios) in trauma resuscitation.
We systematically searched Medline, Embase, Web of Science, Biosis, Cochrane Central, and Scopus.
Two independent reviewers selected randomized controlled trials and observational studies comparing two or more platelet:RBC ratios in trauma resuscitation. We excluded studies investigating the use of whole blood or hemostatic products.
Two independent reviewers extracted data and assessed the risk of bias. Primary outcomes were early (in ICU or within 30 d) and late (in hospital or after 30 d) mortality. Secondary outcomes were multiple organ failure, lung injury, and sepsis.
From 6,123 citations, no randomized controlled trials were identified. We included seven observational studies (4,230 patients) addressing confounders through multivariable regression or propensity scores. Heterogeneity of studies precluded meta-analysis. Among the five studies including exclusively patients requiring massive transfusions, four observed a lower mortality with higher ratios. Two studies considering nonmassively bleeding patients observed no benefit of using higher ratios. Two studies evaluated the implementation of a massive transfusion protocol; only one study observed a decrease in mortality with higher ratios. Of the two studies at low risk of survival bias, one study observed a survival benefit. Three studies assessed secondary outcomes. One study observed an increase in multiple organ failure with higher ratios, whereas no study demonstrated an increased risk in lung injury or sepsis.
There is insufficient evidence to strongly support the use of a precise platelet:RBC ratio for trauma resuscitation, especially in nonmassively bleeding patients. Randomized controlled trials evaluating both the safety and efficacy of liberal platelet transfusions are warranted.
Severe traumatic brain injury often leads to death from withdrawal of life-sustaining therapy, although prognosis is difficult to determine.
To evaluate variation in mortality following the ...withdrawal of life-sustaining therapy and hospital mortality in patients with critical illness and severe traumatic brain injury, we conducted a two-year multicentre retrospective cohort study in six Canadian level-one trauma centres. The effect of centre on hospital mortality and withdrawal of life-sustaining therapy was evaluated using multivariable logistic regression adjusted for baseline patient-level covariates (sex, age, pupillary reactivity and score on the Glasgow coma scale).
We randomly selected 720 patients with traumatic brain injury for our study. The overall hospital mortality among these patients was 228/720 (31.7%, 95% confidence interval CI 28.4%-35.2%) and ranged from 10.8% to 44.2% across centres (χ(2) test for overall difference, p < 0.001). Most deaths (70.2% 160/228, 95% CI 63.9%-75.7%) were associated with withdrawal of life-sustaining therapy, ranging from 45.0% (18/40) to 86.8% (46/53) (χ(2) test for overall difference, p < 0.001) across centres. Adjusted odd ratios (ORs) for the effect of centre on hospital mortality ranged from 0.61 to 1.55 (p < 0.001). The incidence of withdrawal of life-sustaining therapy varied by centre, with ORs ranging from 0.42 to 2.40 (p = 0.001). About one half of deaths that occurred following the withdrawal of life-sustaining therapies happened within the first three days of care.
We observed significant variation in mortality across centres. This may be explained in part by regional variations in physician, family or community approaches to the withdrawal of life-sustaining therapy. Considering the high proportion of early deaths associated with the withdrawal of life-sustaining therapy and the limited accuracy of current prognostic indicators, caution should be used regarding early withdrawal of life-sustaining therapy following severe traumatic brain injury.
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