Critically ill adults are at increased risk of VTE, including DVT, and pulmonary embolism. Various agents exist for venous thromboprophylaxis in this population.
What is the comparative efficacy and ...safety of prophylaxis agents for prevention of VTE in critically ill adults?
Systematic review and network meta-analysis of randomized clinical trials (RCTs) evaluating efficacy of thromboprophylaxis agents among critically ill patients. We searched six databases (including PubMed, EMBASE, and Medline) from inception through January 2021 for RCTs of patients in the ICU receiving pharmacologic, mechanical, or combination therapy (pharmacologic agents and mechanical devices) for thromboprophylaxis. Two reviewers performed screening, full-text review, and extraction. We used the Grading of Recommendations Assessment, Development, and Evaluation to rate certainty of effect estimates.
We included 13 RCTs (9,619 patients). Compared with control treatment (a composite of no prophylaxis, placebo, or compression stockings only), low-molecular-weight heparin (LMWH) reduced the incidence of DVT (OR, 0.59 95% credible interval CrI, 0.33-0.90; high certainty) and unfractionated heparin (UFH) may reduce the incidence of DVT (OR, 0.82 95% CrI, 0.47-1.37; low certainty). LMWH probably reduces DVT compared with UFH (OR, 0.72 95% CrI, 0.46-0.98; moderate certainty). Compressive devices may reduce risk of DVT compared with control treatments; however, this is based on low-certainty evidence (OR, 0.85 95% CrI, 0.50-1.50). Combination therapy showed unclear effect on DVT compared with either therapy alone (very low certainty).
Among critically ill adults, compared with control treatment, LMWH reduces incidence of DVT, whereas UFH and mechanical compressive devices may reduce the risk of DVT. LMWH is probably more effective than UFH in reducing incidence of DVT and should be considered the primary pharmacologic agent for thromboprophylaxis. The efficacy and safety of combination pharmacologic therapy and mechanical compressive devices were unclear.
Open Science Framework; URL: https://osf.io/694aj.
Purpose
In shock, hypotension may contribute to inadequate oxygen delivery, organ failure and death. We conducted the Optimal Vasopressor Titration (OVATION) pilot trial to inform the design of a ...larger trial examining the effect of lower versus higher mean arterial pressure (MAP) targets for vasopressor therapy in shock.
Methods
We randomly assigned critically ill patients who were presumed to suffer from vasodilatory shock regardless of admission diagnosis to a lower (60–65 mmHg) versus a higher (75–80 mmHg) MAP target. The primary objective was to measure the separation in MAP between groups. We also recorded days with protocol deviations, enrolment rate, cardiac arrhythmias and mortality for prespecified subgroups.
Results
A total of 118 patients were enrolled from 11 centres (2.3 patients/site/month of screening). The between-group separation in MAP was 9 mmHg (95 % CI 7–11). In the lower and higher MAP groups, we observed deviations on 12 versus 8 % of all days on vasopressors (
p
= 0.059). Risks of cardiac arrhythmias (20 versus 36 %,
p
= 0.07) and hospital mortality (30 versus 33 %,
p
= 0.84) were not different between lower and higher MAP arms. Among patients aged 75 years or older, a lower MAP target was associated with reduced hospital mortality (13 versus 60 %,
p
= 0.03) but not in younger patients.
Conclusions
This pilot study supports the feasibility of a large trial comparing lower versus higher MAP targets for shock. Further research may help delineate the reasons for vasopressor dosing in excess of prescribed targets and how individual patient characteristics modify the response to vasopressor therapy.
Digitalis toxicity produces a toxidrome characterized by gastrointestinal, neurologic, electrolyte, and nonspecific cardiac manifestations. Chronic toxicity remains much more difficult to recognize ...compared with an acute presentation because of the nonspecific manifestations; therefore, serum glycoside levels are essential for diagnosis in this population. The mainstay of management continues to be rapid toxidrome identification followed by digoxin-specific antibody fragment therapy with supportive care. Several controversies still remain, including therapy for patients dependent on hemodialysis, appropriateness of calcium therapy for hyperkalemia, ideal agents for arrhythmia therapy, and the potential utility of plasmapheresis for removal of bound digoxin-antibody fragment complexes.
ObjectivesPatients often suffer from disturbed sleep in hospital. Poor-quality sleep in hospitalised patients has been associated with significant morbidity and pharmacological sleep aids are often ...prescribed. The objective of this systematic review is to evaluate the comparative efficacy and safety of pharmacological interventions used for sleep in hospitalised patients.Setting/participantsWe searched MEDLINE, Embase, the Cochrane database and grey literature for prospective studies that evaluated sleep in hospitalised adults after a pharmacological intervention.Primary and secondary outcome measuresTwo reviewers assessed studies for inclusion and extracted data for efficacy outcomes, including sleep efficiency, sleep latency, sleep fragmentation and objectively measured sleep stage distribution. Risk of bias was assessed and meta-analyses were planned contingent upon homogeneity of the included studies.ResultsAfter screening 1920 citations, 15 studies involving 861 patients were included. Medications studied included benzodiazepines, nonbenzodiazepine sedatives, melatonin, propofol and dexmedetomidine. Five studies were deemed to be of high quality. Heterogeneity and variable outcome reporting precluded meta-analysis in most cases. No consistent trends with respect to sleep efficiency, quality or interruptions were observed identifying a drug or drug class as superior to another or no treatment. Benzodiazepines appeared to be better than no treatment with respect to sleep latency, but this was not consistently demonstrated across all studies. Sleep stage distribution shows that sleep in hospital is dominated by stages N1 and N2.ConclusionsThere is insufficient evidence to suggest that pharmacotherapy improves the quality or quantity of sleep in hospitalised patients suffering from poor sleep. No drug class or specific drug was identified as superior even when compared to placebo or no treatment. Although 15 studies were included, the quality of evidence was limited by their quality and size. Larger, better-designed trials in hospitalised adults are needed.
The Clinician Scientist Williamson, David R; Kanji, Salmaan; Burry, Lisa
Canadian journal of hospital pharmacy,
2021, Volume:
74, Issue:
2
Journal Article
ObjectivesWe systematically reviewed the literature to identify evidence-informed recommendations regarding the detection of drug-induced pancreatitis (DIP) and, secondarily, to describe clinical ...processes for the diagnosis of DIP.DesignSystematic review.Data sourcesOvid MEDLINE, including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase Classic+Embase, the Cochrane Library.Eligibility criteriaWe included clinical practice guidelines, systematic reviews, narrative reviews and observational studies with a focus of establishing incidence, prevalence or diagnostic approaches for DIP. Clinical trials that diagnosed DIP as an outcome were also included.Data extraction and synthesisTwo reviewers screened citations and performed data extraction. A narrative synthesis of the evidence was prepared.ResultsFifty-nine studies were included. Early published evidence suggested serial pancreatic ultrasound could detect subclinical pancreatitis; however, subsequent studies demonstrated no utility of serial ultrasound or serial monitoring of pancreatic enzymes in the early detection of DIP. Two small studies conducted in patients with a high baseline risk of acute pancreatitis concluded serial monitoring of pancreatic enzymes may be useful to guide early discontinuation of medications with known associations with pancreatitis. Early discontinuation of medication was not advised for lower-risk patients because some medications cause transient elevations of pancreatic enzymes that do not progress to acute pancreatitis. Eight of 52 studies (15%) reporting a clinical diagnostic process for DIP reported using currently accepted criteria for the diagnosis of acute pancreatitis. A variety of methods were used to assess drug-related causality.ConclusionsThere is minimal evidence to support the use of serial monitoring by ultrasound or pancreatic enzymes to detect cases of DIP. Serial monitoring may be useful to guide early discontinuation of DIP-associated drugs in high-risk patients, but not in lower-risk patients. Greater uptake of standardised diagnostic and causality criteria for DIP is needed.Trial registration numberCRD42017060473
To determine the association between non-adherence to long term chronic obstructive pulmonary disease (COPD) medications and COPD related emergency department (ED) visits and hospitalizations in ...patients with incident COPD, utilizing time varying measures of adherence as well as accounting for time-varying confounding impacted by prior adherence.
We conducted a population-based retrospective cohort study between 2007-2017 among individuals aged 66 years and older with incident COPD using multiple linked administrative health databases from the province of Ontario, Canada. Adherence to COPD medications was measured using time varying proportion of days covered based on insurance claims for medications dispensed at community pharmacies. The parametric g-formula was used to assess the association between time-varying adherence (in the last 90-days) to COPD medications and risk of COPD related hospitalizations and ED visits while accounting for time varying confounding by COPD severity.
Overall, 60,251 individuals with incident COPD were included; mean age was 76 (SD 7) and 59% were male. Mean adherence over the entire follow-up was 23% (SD 0.3). There were 7,248 (12%) COPD related ED visits (2.8 events per 100 person years PY) and 9,188 (15%) COPD related hospitalizations (3.5 events per 100 PY). Compared to those with 0% 90-day adherence, those with adherence between 1-33% had a 19% decreased risk of COPD related ED visits (adjusted risk ratioaRR:0.81, 95% confidence interval CI:0.78-0.83), those with adherence between 34%-67% had a 18% decreased risk (aRR: 0.82, 95% CI: 0.77-0.85) while those with 68%-100% 90-day adherence had a 63% increased risk of COPD related ED visits (aRR: 1.63, 95% CI: 1.47-1.78). Nearly identical results were obtained for COPD specific hospitalizations.
After accounting for time varying confounding by COPD severity, the highest time varying 90-days adherence was associated with an increased risk of both COPD related ED visits and hospitalizations compared to the lowest adherence categories. Differences in COPD severity between adherence categories, perception of need for medication management in the higher adherence categories, and potential residual confounding makes it difficult to disentangle the independent effects of adherence from the severity of the condition itself.
Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney ...replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion.
To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings.
We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible.
The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported.
Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol.
The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes.
This systematic review protocol is registered at PROSPERO, CRD42018101955.
OBJECTIVES:Accurate prognostic information in patients with severe traumatic brain injury remains limited, but mortality following the withdrawal of life-sustaining therapies is high and variable ...across centers. We designed a survey to understand attitudes of physicians caring for patients with severe traumatic brain injury toward the determination of prognosis and clinical decision making on the level of care.
DESIGN, SETTING, AND PARTICIPANTS:We conducted a cross-sectional study of intensivists, neurosurgeons, and neurologists that participate in the care of patients with severe traumatic brain injury at all Canadian level 1 and level 2 trauma centers.
INTERVENTION:None.
MEASUREMENTS:The main outcome measure was physicians’ perceptions of prognosis and recommendations on the level of care.
MAIN RESULTS:Our response rate was 64% (455/712). Most respondents (65%) reported that an accurate prediction of prognosis would be most helpful during the first 7 days. Most respondents (>80%) identified bedside monitoring, clinical exam, and imaging to be useful for evaluating prognosis, whereas fewer considered electrophysiology tests (<60%) and biomarkers (<15%). In a case-based scenario, approximately one-third of respondents agreed, one-third were neutral, and one-third disagreed that the patient prognosis would be unfavorable at one year. About 10% were comfortable recommending withdrawal of life-sustaining therapies.
CONCLUSIONS:A significant variation in perceptions of neurologic prognosis and in clinical decision making on the level of care was found among Canadian intensivists, neurosurgeons, and neurologists. Improved understanding of the factors that can accurately predict prognosis for patients with traumatic brain injury is urgently needed.
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