Clinical and survival differences during separate COVID-19 surges: Investigating the impact of the Sars-CoV-2 alpha variant in critical care patients.

A number of studies have highlighted physiological data from the first surge in critically unwell Covid-19 patients but there is a paucity of data describing emerging variants of SARS-CoV-2, such as B.1.1.7. We compared ventilatory parameters, biochemical and physiological data and mortality between the first and second COVID-19 surges in the United Kingdom, where distinct variants of SARS-CoV-2 were the dominant stain. We performed a retrospective cohort study investigating critically unwell patients admitted with COVID-19 across three tertiary regional ICUs in London, UK. Of 1782 adult ICU patients screened, 330 intubated and ventilated patients diagnosed with COVID-19 were included. In the second wave where B.1.1.7 variant was the dominant strain, patients were had increased severity of ARDS whilst compliance was greater (p<0.05) and d-dimer lower. The 28-day mortality was not statistically significant (1st wave: 42.2% vs 2nd wave: 39.8%). However, when adjusted for key covariates, the hazard ratio for 28-day mortality in those patients with B.1.1.7 was 3.79 (CI 1.04-13.8; p = 0.043) compared to the original strain. During the second surge in the UK, where the COVID-19 variant B.1.1.7 was most prevalent, significantly more patients presented to critical care with severe ARDS. Furthermore, mortality risk was significantly greater in our ICU population during the second wave of the pandemic in those patients with B.1.1.7. As ICUs are experiencing further waves (particularly by the delta (B.1.617.2) variant), we highlight the urgent need for prospective studies describing immunological and pathophysiological differences across novel emerging variants.

Randomised trials of human albumin for adults with sepsis: systematic review and meta-analysis with trial sequential analysis of all-cause mortality.

OBJECTIVE: To assess the efficacy and safety of pooled human albumin solutions as part of fluid volume expansion and resuscitation (with or without improvement of baseline hypoalbuminaemia) in critically unwell adults with sepsis of any severity. DESIGN: Systematic review and meta-analysis of randomised clinical trials, with trial sequential analysis, subgroup, and meta-regression analyses. DATA SOURCES: PubMed, PubMed Central, Web of Science (includes Medline, Conference Proceedings Citation Index, Data Citation Index, Chinese Science Citation Database, CAB abstracts, Derwent Innovations Index), OvidSP (includes Embase, Ovid Medline, HMIC, PsycINFO, Maternity and Infant Care, Transport Database), Cochrane Library, clinicaltrials.gov, controlled-trials.com, online material, relevant conference proceedings, hand searching of reference lists, and contact with authors as necessary. ELIGIBILITY CRITERIA: Prospective randomised clinical trials of adults with sepsis of any severity (with or without baseline hypoalbuminaemia) in critical or intensive care who received pooled human albumin solutions as part of fluid volume expansion and resuscitation (with or without improvement of hypoalbuminaemia) compared with those who received control fluids (crystalloid or colloid), were included if all-cause mortality outcome data were available. No restriction of language, date, publication status, or primary study endpoint was applied. DATA EXTRACTION: Two reviewers independently assessed articles for inclusion, extracted data to assess risk of bias, trial methods, patients, interventions, comparisons, and outcome. The relative risk of all-cause mortality was calculated using a random effects model accounting for clinical heterogeneity. PRIMARY OUTCOME MEASURE: All-cause mortality at final follow-up. RESULTS: Eighteen articles reporting on 16 primary clinical trials that included 4190 adults in critical or intensive care with sepsis, severe sepsis, or septic shock. A median of 70.0 g daily of pooled human albumin was received over a median of 3 days by adults with a median age of 60.8 years as part of fluid volume expansion and resuscitation, with or without correction of hypoalbuminaemia. The relative risk of death was similar between albumin groups (that received a median of 175 g in total) and control fluid groups (relative risk 0.94; 95% confidence interval 0.87 to 1.01; P=0.11; I(2)=0%). Trial sequential analysis corrected the 95% confidence interval for random error (0.85 to 1.02; D(2)=0%). Eighty eight per cent of the required information size (meta-analysis sample size) of 4894 patients was achieved, and the cumulative effect size measure (z score) entered the futility area, supporting the notion of no relative benefit of albumin (GRADE quality of evidence was moderate). Evidence of no difference was also found when albumin was compared with crystalloid fluid (relative risk 0.93; 0.86 to 1.01; P=0.07; I(2)=0%) in 3878 patents (GRADE quality of evidence was high; 79.9% of required information size) or colloid fluids in 299 patients (relative risk 1.04; 0.79 to 1.38; P=0.76; I(2)=0%) (GRADE quality of evidence was very low; 5.8% of required information size). When studies at high risk of bias were excluded in a predefined subgroup analysis, the finding of no mortality benefit remained, and the cumulative z score was just outside the boundary of futility. Overall, the meta-analysis was robust to sensitivity, subgroup, meta-regression, and trial sequential analyses. CONCLUSIONS: In this analysis, human albumin solutions as part of fluid volume expansion and resuscitation for critically unwell adults with sepsis of any severity (with or without baseline hypoalbuminaemia) were not robustly effective at reducing all-cause mortality. Albumin seems to be safe in this setting, as a signal towards harm was not detected, but this analysis does not support a recommendation for use.

Poor analgesic efficacy of epidural analgesia in critical care patients after pancreaticoduodenectomy.

OBJECTIVES: The objective of this study was to investigate the analgesic efficacy of functional and prematurely aborted epidurals after pancreaticoduodenectomy in critical care, as this is unknown. METHODS: Data from elective pancreaticoduodenectomy recipients admitted to the critical care unit over 44 months were prospectively collected. Epidural (0.1% bupivacaine and 2 µg/mL fentanyl) analgesic efficacy was assessed with a ranked categorical verbal pain score (primary end point). If no epidural was placed, intravenous (IV) fentanyl patient-controlled analgesia (PCA) was used. RESULTS: Eighty-six pancreaticoduodenectomy patients had a mean age of 66.5 years; 61.6% were men; and 73 received an epidural, whereas 13 received an IV PCA. Epidural abortion rate was 42.5%, associated with a higher 24-hour (P = 0.02) but not 48-hour pain score. Overall, fewer patients reported any pain (P = 0.010; number needed to harm, 3.2; 95% confidence interval, 1.7-3.2) or severe pain (P = 0.006; number needed to harm, 2.9; 95% confidence interval, 2.1-4.7) with functional epidurals. Pain (sensitivity, 93.8%) and severe pain (specificity, 87.8%) were predictive of epidural abortion. Most postepidural analgesia was IV PCA (P = 0.097) after both functional and aborted epidurals. CONCLUSIONS: Premature epidural abortion rate was high and associated with analgesic morbidity. Pain score was predictive of epidural abortion. Thus, preference toward epidural analgesia cannot be supported.

Randomised trials of 6% tetrastarch (hydroxyethyl starch 130/0.4 or 0.42) for severe sepsis reporting mortality: systematic review and meta-analysis.

PURPOSE: To assess the impact of 6% tetrastarch [hydroxyethyl starch (HES) 130/0.4 and 130/0.42] in severe sepsis patients. The primary outcome measure was 90-day mortality. METHODS: A structured literature search was undertaken to identify prospective randomised controlled trials (RCTs) in adult patients with severe sepsis receiving 6% tetrastarch (of potato or waxy maize origin) as part of fluid resuscitation in comparison with other non-HES fluids after randomisation in the critical care setting. A systematic review and meta-analysis were performed. RESULTS: Six RCTs were included (n = 3,033): three from 2012 (n = 2,913) had low risk of bias. Median tetrastarch exposure was 37.4 ml/kg (range 30-43 ml/kg). Ninety-day mortality was associated with tetrastarch exposure [relative risk (RR) 1.13; 95% confidence interval (CI) 1.02-1.25; p = 0.02] compared with crystalloid. The number needed to harm (NNH) was 28.8 (95 % CI 14.6-942.5). Publication bias and statistical heterogeneity (I(2) = 0%) were not present. Tetrastarch exposure was also associated with renal replacement therapy (p = 0.01; NNH 15.7) and allogeneic transfusion support (p = 0.001; NNH 9.9). No difference between groups was observed for 28-day mortality, for comparison with colloid as control, or for waxy maize-derived tetrastarch, but power was lacking. Overall mortality was associated with tetrastarch exposure (RR 1.13; 95% CI 1.02-1.25; p = 0.02). CONCLUSIONS: In our analysis, 6% tetrastarch as part of initial fluid resuscitation for severe sepsis was associated with harm and, as alternatives exist, in our view should be avoided.

Successful removal of malpositioned chest drain within the liver by embolization of the transhepatic track.

The insertion of a chest drain catheter for the management of a pneumothorax in an 82-year-old woman resulted in the unusual complication of liver penetration. The position of the drain was assessed by contrast-enhanced computed tomographic scan. Because the patient was hemodynamically stable and no damage to major vessels was seen on computed tomographic scan, the patient was treated in a nonoperative manner. A procedure was performed under controlled conditions using techniques used during transhepatic liver biopsies but with the addition of a balloon catheter. Embolization of the liver track was performed during chest drain removal. The drain was successfully removed without the complication of bleeding in a patient unsuitable for a general anesthetic.

Mannose-binding lectin polymorphisms in severe sepsis: relationship to levels, incidence, and outcome.

Mannose-binding lectin (MBL) genetic polymorphisms result in deficiency of the encoded protein and increased susceptibility to infection, especially in children and the immunocompromised. The objective of this study was to investigate the relationship between MBL-2 exon 1 and promoter -221 polymorphisms, plasma levels of the encoded protein, and the incidence and outcome of severe sepsis and septic shock. One hundred seventy-four white adult patients with severe sepsis or septic shock were recruited in a prospective multicenter study across eight intensive care units in the South of England, UK. Genotype and haplotype frequencies were compared between normal population controls and patients, and between survivors and nonsurvivors. Plasma levels of encoded protein were related to genotype and outcome. The exon 1 polymorphisms (A/O or O/O) were significantly more common in the patients with severe sepsis and septic shock than in normal healthy adults (54.6% vs. 39.7%, P = 0.001), and there was a significant difference in haplotype frequency between controls and septic patients (P < 0.0001). There was no significant difference in MBL-2 genotype or haplotype frequency between survivors and nonsurvivors. There was a strong relationship between MBL-2 haplotype and plasma MBL concentration (P < 0.001). Individual plasma levels were variable and increased between days 1 and 7. The mortality rate was higher in those with MBL levels <1000 microg/L than in those patients with levels >1000 microg/L (47.2 vs. 22.2%, P = 0.05). We conclude that genetic polymorphisms resulting in mannose-binding lectin deficiency are associated with increased susceptibility to sepsis. The close relationship between polymorphic variants and plasma MBL concentration persists during sepsis but individual levels vary widely. Lower circulating MBL levels are associated with a poor outcome.