Objective:
To describe the effect of inhaled prostaglandins on both oxygenation and mortality in critically ill patients with acute respiratory distress syndrome (ARDS), with a focus on safety and ...efficacy in coronavirus disease 2019 (COVID-19)-associated ARDS and non-COVID-19 ARDS.
Data Sources:
A literature search of MEDLINE was performed using the following search terms: inhaled prostaglandins, inhaled epoprostenol, inhaled nitric oxide, ARDS, critically ill. All abstracts were reviewed.
Study Selection and Data Extraction:
Relevant English-language reports and studies conducted in humans between 1980 and June 2023 were considered.
Data Synthesis:
Data regarding inhaled prostaglandins and their effect on oxygenation are limited but show a benefit in patients who respond to therapy, and data pertaining to their effect on mortality is scarce. Concerns exist regarding the formulation of inhaled epoprostenol (iEPO) utilized in addition to modes of medication delivery; however, the limited data surrounding their use have shown a reasonable safety profile. Other avenues and beneficial effects may exist with inhaled prostaglandins, such as use in COVID-19-associated ARDS or non-COVID-19 ARDS patients undergoing noninvasive mechanical ventilation or during patient transport.
Relevance to Patient Care and Clinical Practice:
The use of inhaled prostaglandins can be considered in critically ill patients with COVID-19-associated ARDS or non-COVID-19 ARDS who are experiencing difficulties with oxygenation refractory to nonpharmacologic strategies.
Conclusions:
The use of iEPO and other inhaled prostaglandins requires further investigation to fully elucidate their effects on clinical outcomes, but it appears these medications may have a potential benefit in COVID-19-associated ARDS and non-COVID-19 ARDS patients with refractory hypoxemia but with little effect on mortality.
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•The majority of patients received fixed dose (10 units) IV insulin for hyperkalemia.•Hypoglycemia was not different between fixed and reduced dosing groups.•Patient weight and pre-insulin glucose ...may contribute to hypoglycemia risk.•IV insulin dosing for hyperkalemia should be individualized.
While intravenous (IV) insulin is often administered at a fixed dose of 10 units for acute hyperkalemia, optimal dosing for minimizing hypoglycemia while effectively reversing hyperkalemia has not been established. The purpose of this analysis was to evaluate the effect of insulin dosing strategies on hypoglycemia in patients with hyperkalemia.
Adult patients presenting to an academic medical center who received IV insulin for hyperkalemia between 2016 and 2020 were retrospectively identified. Patients treated with 10 units of insulin (fixed) were compared to those who received < 10 units (reduced). The primary outcome was the incidence of hypoglycemia (blood glucose < 70 mg/dL) within 12 hours of insulin administration. Secondary outcomes included the incidence of severe hypoglycemia (blood glucose < 40 mg/dL) and change in potassium. Multivariable analyses were used to assess for risk factors for hypoglycemia and severe hypoglycemia.
Of the 2576 patients included, 305 (11.8%) received reduced dosing and 2271 (88.2%) received fixed dosing. Hypoglycemia occurred in 16.7% of the reduced group and 15.9% of the fixed group (P = 0.70). Severe hypoglycemia occurred in 2.3% of the reduced group and 2.5% of the fixed group (P = 0.86). Median potassium reduction from baseline to first check post-insulin was less with reduced dosing (−0.6 mEq/L vs −0.8 mEq/L, P < 0.001). On multivariable regression analysis, greater weight-based insulin dose and ED location were significant predictors for hypoglycemia and severe hypoglycemia. Location in the intensive care unit was associated with a decreased risk of hypoglycemia. Higher pre-insulin glucose was protective for hypoglycemia and severe hypoglycemia.
The incidence of hypoglycemia was similar among both groups. Greater weight-based insulin dose was a significant risk factor for hypoglycemia, while higher baseline glucose levels were associated with a decreased risk, indicating that patient-specific insulin dosing for hyperkalemia may be warranted.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background:
An impaired sleep-wake cycle may be one factor that affects the development of delirium in critically ill patients. Several small studies suggest that exogenous melatonin or ramelteon may ...decrease the incidence and/or duration of delirium.
Objective:
To compare the effect of prophylactic administration of melatonin, ramelteon, or no melatonin receptor agonist on the development of delirium in the intensive care unit (ICU).
Methods:
This was a single-center, retrospective, observational cohort study of nondelirious patients in the ICU who received melatonin, ramelteon, or no melatonin receptor agonist. The primary end point was the incidence of delirium. Secondary end points included assessments of daily level of sedation and daily utilization of antipsychotic, sedative, and opioid agents.
Results:
No difference was observed in the incidence of delirium among the melatonin, ramelteon, and placebo cohorts (18.7% vs 14.3% vs 13.8%; P = 0.77). A difference was observed in the rate of agitation and sedation among the 3 groups, with the greatest observed in the melatonin cohort. Additionally, there was a difference in the use of propofol, dexmedetomidine, and opioids. Overall, there was no difference in clinical outcomes, including duration of mechanical ventilation and ICU or hospital length of stay.
Conclusion and Relevance:
Therapy with melatonin, ramelteon, and no melatonin receptor agonist resulted in similar rates of delirium in a mixed ICU population. Despite significant differences in agitation, sedation, and medication utilization, there was no differences in the clinical outcomes evaluated.
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Introduction
Sedatives and analgesics are commonly utilized as continuous infusions in the ICU but have complications, including an increase in mechanical ventilation days, ICU length of stay, and ...delirium. Atypical antipsychotics (AAPs) affect several receptors including muscarinic, histamine, and α-1 adrenergic receptors, which may allow them to act as adjunctive agents to facilitate weaning of continuous infusions.
Objective
To determine if there is a decrease in sedatives/analgesics requirements with the use of quetiapine and olanzapine in mechanically ventilated critically ill patients.
Methods
A single-center, retrospective study conducted at Brigham and Women's Hospital from 1/1/2018 to 12/31/2019. Patients were included if they were mechanically ventilated for at least 48 hours before and following AAP initiation, were receiving at least one sedative/analgesic by continuous infusion and received AAP for at least 48 hours. The major endpoint was the percentage of patients with ≥20% reduction in the cumulative dose (CD) of midazolam, propofol, or opioids using morphine mg equivalent (MME), 48 hours from AAP initiation. Minor endpoints included median changes in CD at 24 and 48 hours, and Richmond Agitation–Sedation Scale (RASS), and Critical Care Pain Observation Tool (CPOT) changes at 48 hours.
Results
A total of 1177 encounters were screened and 107 were included. Within the 48 hours after AAP initiation, 77.6% had ≥20% reduction in the CD of a sedative/analgesic. There was a significant reduction in propofol, no change in MME, and significant increase in dexmedetomidine median CD at 48 hours from AAP start. No difference was found in pain scores, but patients had significantly lighter sedation scores in the 48 hours after AAP initiation. A multivariate analysis showed that earlier initiation of antipsychotics was associated with a higher likelihood of achieving a 20% reduction in a sedative/analgesic.
Conclusion
AAP use was associated with a significant reduction in sedatives/analgesics doses. Future studies are warranted to confirm the results.
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Background
Vasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of ...the combination.
Objective
This study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients.
Methods
This was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the “early” group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the “late” group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation.
Results
A total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group.
Conclusion and relevance
Our study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.
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Background:
Opioid-induced constipation (OIC) may occur in up to 81% of critically ill patients and can lead to many complications. Opioid antagonists are a reasonable approach and may be used for ...managing OIC.
Objective:
The purpose of this study was to assess the efficacy of enteral naloxone (NLX) versus subcutaneous methylnaltrexone (MNTX) for the management of OIC in critically ill patients.
Methods:
A retrospective analysis was conducted on adult patients who received NLX or MNTX and a continuous opioid infusion for at least 48 hours. The primary end point was time to resolution of constipation, defined as hours to first bowel movement (BM) after the first dose of an opioid antagonist. Reversal of analgesia was assessed by comparing the total number of morphine milligram equivalents (MME) 24 hours preopioid and postopioid antagonist administration. Univariate and multivariate analyses were conducted to assess treatment response within 48 hours.
Results:
Baseline characteristics were similar between patients receiving NTX (n = 89) and MNTX (n = 71). However, the time to the first BM with NLX was 18 hours compared with 41 hours with MNTX (P = 0.004). There was no difference in MME requirements 24 hours pre/post NLX or MNTX administration. Naloxone administration was identified as a statistically significant predictor of BM within 48 hours (odds ratio OR = 2.68 1.33-5.38).
Conclusion and Relevance:
The time to first BM was shorter with enteral NLX. Both NLX and MNTX appear to be effective for the management of OIC without causing reversal of analgesia. Future controlled, prospective trials comparing these agents are warranted.
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Abstract Purpose The objective of this study was to evaluate the use of sedative, analgesic, and neuromuscular blocking agents (NMBAs) in patients undergoing ECMO support. Materials and methods This ...was a two year, prospective, observational study of adult ICU patients on ECMO support for more than 48 hours. Results We analyzed 32 patients, including 15 VA ECMO and 17 VV ECMO. The median daily dose of benzodiazepines (midazolam equivalents) was 24 mg and the median daily dose of opioids (fentanyl equivalents) was 3875 mcg. There was a moderate negative correlation between the day of ECMO and the median daily benzodiazepine dose (r = −0.5515) and a very weak negative correlation for the median daily opioid dose (r = −0.0053). On average patients were sedated to RASS scores between 0 and −1. Continuous infusions of opioids, benzodiazepines, propofol, dexmedetomidine, and neuromuscular blocking agents were administered on 404 (85.1%), 199 (41.9%), 95 (20%), 32 (6.7%), and 60 (12.6%) ECMO days, respectively. Patients in the VA arm received a continuous infusion opioid (96.4% vs. 81.6% days, P < .001) and benzodiazepine (58.2% vs. 37.0% days, P < .001) more frequently. Conclusions Patients received relatively low doses of sedatives and analgesics while at a light level of sedation on average. Patients rarely required neuromuscular blockade.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In this single-center, retrospective cohort analysis of hospitalized coronavirus disease 2019 (COVID-19) patients, we investigate whether inflammatory biomarker levels predict respiratory decline in ...patients who initially present with stable disease. Examination of C-reactive protein (CRP) trends reveals that a rapid rise in CRP levels precedes respiratory deterioration and intubation, although CRP levels plateau in patients who remain stable. Increasing CRP during the first 48 h of hospitalization is a better predictor (with higher sensitivity) of respiratory decline than initial CRP levels or ROX indices (a physiological score of respiratory function). CRP, the proinflammatory cytokine interleukin-6 (IL-6), and physiological measures of hypoxemic respiratory failure are correlated, which suggests a mechanistic link. Our work shows that rising CRP predicts subsequent respiratory deterioration in COVID-19 and may suggest mechanistic insight and a potential role for targeted immunomodulation in a subset of patients early during hospitalization.
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Rising CRP levels predict intubation in COVID-19 inpatients stable at admissionEarly CRP trend outperforms initial CRP level in prediction of respiratory failureCRP trend outperforms a physiological index (ROX) in prediction of respiratory failureCRP and IL-6 levels correlate with each other and with hypoxemia (PaO2/FiO2)
Mueller et al. demonstrate in hospitalized COVID-19 patients that trending C-reactive protein (CRP), an inflammatory biomarker, is a simple and accessible strategy for predicting respiratory deterioration. An early rise in CRP predicts intubation, and CRP levels correlate with IL-6 levels and physiological measures of hypoxemic respiratory failure.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The purpose of this analysis is to describe the safety of propofol administration in adult extracorporeal membrane oxygenation (ECMO) patients. We performed a prospective cohort analysis of patients ...using ECMO at Brigham and Womenʼs Hospital between February 2013 and October 2015. Patients were included if they used ECMO for at least 48 hours. The major end-point of the analysis was the median oxygenator lifespan. Oxygenator exchanges were analyzed by the number of patients requiring an oxygenator exchange and the number of oxygenator exchanges per ECMO day. A priori analysis was performed by comparing the outcomes between patients who did and did not receive propofol during their ECMO course. During the study, 43 patients were included in the analysis. Sixteen patients used propofol during their ECMO course. There were 12 oxygenator exchanges during therapy. Oxygenator exchange occurred on 1.8% of ECMO days. The median oxygenator lifespan was 7 days. Patients who used propofol had a significantly longer oxygenator lifespan (p = 0.02). Among patients who received propofol, patients who required oxygenator exchange used a significantly lower median daily dose of propofol (p < 0.001). The use of propofol appears safe in ECMO with regards to oxygenator viability. Contrary to expected, oxygenator lifespan was significantly longer among patients who received propofol.
Antiepileptics used for seizure prophylaxis after traumatic brain injury (TBI) are reviewed.
Of the 275,000 people who are hospitalized with TBI each year, approximately 5-7% experience a ...posttraumatic seizure (PTS). According to the latest guidelines issued by the Brain Trauma Foundation and the American Academy of Neurology (AAN) for the management of severe TBI, PTS prophylaxis is recommended only during the first seven days after TBI. Of the available antiepileptic drugs, phenytoin has been the most extensively studied for the prophylaxis of PTS. Phenobarbital, valproate, and carbamazepine have not been as extensively researched, and, given their adverse-effect profiles and pharmacodynamic properties, there is no advantage to using these agents over phenytoin. Levetiracetam has demonstrated comparable efficacy to phenytoin for PTS prophylaxis and is associated with fewer adverse effects and monitoring considerations; it may be a reasonable alternative to phenytoin. However, levetiracetam has been associated with an increased seizure tendency. The Brain Trauma Foundation recommends using phenytoin for early PTS prophylaxis. The guidelines also state that valproate has demonstrated similar efficacy to phenytoin but warn that its use may be associated with increased mortality.
The available literature supports the use of antiepileptics for early PTS prophylaxis during the first week after a TBI. Phenytoin has been extensively studied for this indication and is recommended by the AAN and Brain Trauma Foundation guidelines for early PTS prophylaxis. Levetiracetam has demonstrated comparable efficacy to phenytoin for early PTS prophylaxis and may be a reasonable alternative to consider in this patient population.
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DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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