Safety and Feasibility of Opening Tamsulosin Capsules for Enteral Feeding Tube Administration.

Purpose: Tamsulosin is formulated as sustained release beads within a capsule to prevent rapid absorption and associated hypotension. The package insert advises the capsule is swallowed whole; not crushed, chewed, or opened. To our knowledge, there are no current data on opening capsules for adults with enteral tube feeds. Given the unidentified safety and efficacy of administration via enteral tubes, alternative alpha blockers with less selectivity for alpha1A are often used. Methods: A single center retrospective chart review was conducted at two hospital sites. Adult patients that received at least one dose of tamsulosin or doxazosin while an enteral feeding tube was placed were included. Safety outcomes evaluated were the number of documented tube obstructions and incidence of medication associated hypotension. Results: 169 patients were included. Ten enteral feeding tube obstructions were reported, 4 of 110 (3.64%) in the tamsulosin arm and 6 of 59 (10.17%) in the doxazosin arm (RR .36, 95% CI .11 to 1.22, P = .099). At least 1 episode of medication associated hypotension occurred in 22 of 98 (22.45%) in the tamsulosin arm and 20 of 49 (40.82%) in the doxazosin arm (RR .55, 95% CI .33 to .91, P = .019). Conclusion: There was no statistically significant difference in the number of tube obstructions between patients receiving tamsulosin or doxazosin via enteral tube feeds. Patients receiving doxazosin were at increased risk of experiencing medication related hypotension. Tamsulosin capsules may be opened and administered via enteral feeding tubes if administered with content integrity intact.

Single Dose of Sodium Zirconium Cyclosilicate Versus Sodium Polystyrene Sulfonate in Hospitalized Patients With Hyperkalemia.

BACKGROUND: Sodium zirconium cyclosilicate (SZC) is an inorganic zirconium silicate compound that selectively exchanges potassium for hydrogen and sodium. "Once" doses of SZC (with option to redose) in patients with hyperkalemia in hospitalized settings have not been evaluated. We hypothesized that a once dose of SZC would be non-inferior to sodium polystyrene sulfonate (SPS) in reducing serum potassium. OBJECTIVE: The objective of our study is to evaluate the effect of a "once" dose of SZC when compared with SPS in reducing serum potassium levels. METHODS: This was a retrospective analysis of patients who received either a "once" dose of SZC or single or repeated doses of SPS for hyperkalemia. The primary endpoint was mean absolute reduction in the first serum potassium value at least 4 hours after administration. The secondary efficacy endpoints were the rate of additional potassium-lowering therapies and the rate of normokalemia within 48 hours. Safety endpoints were the incidence of electrolyte abnormalities, hypoglycemia, hypertension, hypotension, and colonic necrosis. RESULTS: A total of 260 patients were included in the analysis. The mean initial serum potassium was similar between groups (5.6 ± 0.4). The absolute serum potassium reduction was -0.88 ± 0.64 mEq/L and -0.75 ± 0.65 mEq/L with SZC and SPS, respectively. The "once" regimen of SZC demonstrated non-inferiority compared with SPS (P < 0.0001). The proportion of patients achieving normokalemia within 48 hours and the proportion of patients receiving additional potassium-lowering therapies did not differ between groups. CONCLUSION AND RELEVANCE: The "once" dose regimen (with redose option) of SZC was non-inferior to the "once" or repeated dosing regimen of SPS with regard to absolute potassium reduction. There were no significant differences in the rate of additional potassium-lowering therapies and the rate of normokalemia at 48 hours. The incidence of hypertension was less common among patients who received SZC.

Corticosteroid use in ARDS and its application to evolving therapeutics for coronavirus disease 2019 (COVID-19): A systematic review.

Data regarding the use of corticosteroids for treatment of acute respiratory distress syndrome (ARDS) are conflicting. As the coronavirus disease 2019 (COVID-19) pandemic progresses, more literature supporting the use of corticosteroids for COVID-19 and non-COVID-19 ARDS have emerged. Glucocorticoids are proposed to attenuate the inflammatory response and prevent progression to the fibroproliferative phase of ARDS through their multiple mechanisms and anti-inflammatory properties. The purpose of this systematic review was to comprehensively evaluate the literature surrounding corticosteroid use in ARDS (non-COVID-19 and COVID-19) in addition to a narrative review of clinical considerations of corticosteroid use in these patient populations. OVID Medline and EMBASE were searched. Randomized controlled trials evaluating the use of corticosteroids for COVID-19 and non-COVID-19 ARDS in adult patients on mortality outcomes were included. Risk of bias was assessed with the Risk of Bias 2.0 tool. There were 388 studies identified, 15 of which met the inclusion criteria that included a total of 8877 patients. The studies included in our review reported a mortality benefit in 6/15 (40%) studies with benefit being seen at varying time points of mortality follow-up (ICU survival, hospital, and 28 and 60 days) in the COVID-19 and non-COVID-19 ARDS studies. The two non-COVID19 trials assessing lung injury score improvements found that corticosteroids led to significant improvements with corticosteroid use. The number of mechanical ventilation-free days significantly were found to be increased with the use of corticosteroids in all four studies that assessed this outcome. Corticosteroids are associated with improvements in mortality and ventilator-free days in critically ill patients with both COVID-19 and non-COVID-19 ARDS, and evidence suggests their use should be encouraged in these settings. However, due to substantial differences in the corticosteroid regimens utilized in these trials, questions still remain regarding the optimal corticosteroid agent, dose, and duration in patients with ARDS.

Analgosedation: The Use of Fentanyl Compared to Hydromorphone.

BACKGROUND: The 2018 Society of Critical Care Medicine guidelines on the "Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU" advocate for protocol-based analgosedation practices. There are limited data available to guide which analgesic to use. This study compares outcomes in patients who received continuous infusions of fentanyl or hydromorphone as sedative agents in the intensive care setting. METHODS: This retrospective cohort study evaluated patients admitted into the medical intensive care unit, the surgical intensive care unit, and the cardiac intensive care unit from April 1, 2017, to August 1, 2018, who were placed on continuous analgesics. Patients were divided according to receipt of fentanyl or hydromorphone as a continuous infusion as a sedative agent. The primary endpoints were ICU length of stay and time on mechanical ventilation. RESULTS: A total of 177 patients were included in the study; 103 received fentanyl as a continuous infusion, and 74 received hydromorphone as a continuous infusion. Baseline characteristics were similar between groups. Patients in the hydromorphone group had deeper sedation targets. Median ICU length of stay was eight days in the fentanyl group compared to seven days in the hydromorphone group (p = 0.11) and median time on mechanical ventilation was 146.47 hours in the fentanyl group and 122.33 hours in the hydromorphone group (p = 0.31). There were no statistically significant differences in the primary endpoints of ICU length of stay and time on mechanical ventilation between fentanyl and hydromorphone for analgosedation purposes. CONCLUSION: No statistically significant differences were found in the primary endpoints studied. Patients in the hydromorphone group required more tracheostomies, restraints, and were more likely to have a higher proportion of Critical Care Pain Observation Tool (CPOT) scores > 2.

Does Switching Norepinephrine to Phenylephrine in Septic Shock Complicated by Atrial Fibrillation With Rapid Ventricular Response Improve Time to Rate Control?

BACKGROUND: Atrial fibrillation (AF) frequently develops during critical illness. In septic shock complicated by rapid AF, the use of phenylephrine may be advantageous secondary to its ß-1 sparing properties. However, evidence supporting this strategy is lacking. OBJECTIVE: The purpose of this study is to determine the clinical effect on rate control of transitioning norepinephrine to phenylephrine in septic shock patients who develop AF with a rapid ventricular response (RVR). METHODS: A single-center retrospective study of septic shock patients admitted to the medical or surgical intensive care unit (ICU) who developed AF with RVR (heart rate >110 beats per minute [bpm]). Patients who were switched to phenylephrine were compared to those who remained on norepinephrine. The primary end point was sustained achievement of rate control. A time-varying Cox proportional hazards model was used to assess the primary end point. RESULTS: A total of 67 patients were included in the study, of which 28 were switched to phenylephrine. Baseline characteristics were similar between groups. The unadjusted hazard ratio for achieving rate control was significant at 1.99 (95% confidence interval [CI]: 1.19-3.34; P < .01) for the phenylephrine group. The adjusted hazard ratio was 1.75 (95% CI: 0.86-3.53; P = .12). There were no statistically significant differences in mortality or ICU length of stay. CONCLUSION: Our study suggests a potential clinical effect on achieving rate control when switching to phenylephrine cannot be excluded. It remains unclear if there is a benefit on mortality or length of stay outcomes in critically ill patients.

Safety and feasibility of crushing sevelamer tablets for enteral feeding tube administration.

WHAT IS KNOWN AND OBJECTIVE: Sevelamer is an insoluble polymer indicated for the management of hyperphosphatemia in patients with chronic kidney disease (CKD). The package inserts for both tablet formulations recommend the tablets be administered whole. Due to whole tablets being sometimes inadvertently crushed and the significantly increased cost of sevelamer packets, we evaluated the safety and feasibility of crushed sevelamer tablets for enteral feeding tube administration. METHODS: A single-centre retrospective chart review was performed. All adult ICU patients prescribed sevelamer carbonate between 1 January 2015 and 31 July 2019 were included if they received at least one dose of a sevelamer tablet or packet, whereas they had an enteral feeding tube in place. The primary outcome was the incidence of an obstructed enteral feeding tube or need for replacement, as defined as the number of occurrences over the total numbers of doses administered. The secondary outcome was the change in phosphorus levels from time of sevelamer initiation to discontinuation or patient discharge. RESULTS: A total of 14 obstructions were reported, four in the tablet arm and ten in the packet arm (0.4% tablet arm, 0.5% packet arm; P = .5931). Of these, four (29%) required tube replacement and were followed by sevelamer discontinuation. Two (14%) were documented to be due to increased tube feeds and esomeprazole. Six (43%) cases required tube replacement, but no issues arose upon continuation. Only one of the obstructions resulted in a recurrent tube occlusion. WHAT IS NEW AND CONCLUSION: Sevelamer tablets may be crushed and administered via enteral feeding tubes, provided clear instruction on tablet preparation is included. Oral administration in dysphagic patients requires further evaluation with clear protocols for preparation and administration.

Analgesia and Sedation Strategies in Mechanically Ventilated Adults with COVID-19.

Evidence-based management of analgesia and sedation in COVID-19-associated acute respiratory distress syndrome remains limited. Non-guideline recommended analgesic and sedative medication regimens and deeper sedation targets have been employed for patients with COVID-19 due to exaggerated analgesia and sedation requirements with extended durations of mechanical ventilation. This, coupled with a desire to minimize nurse entry into COVID-19 patient rooms, marked obesity, altered end-organ function, and evolving medication shortages, presents numerous short- and long-term challenges. Alternative analgesic and sedative agents and regimens may pose safety risks and require judicious bedside management for appropriate use. The purpose of this commentary is to provide considerations and solutions for designing safe and effective analgesia and sedation strategies for adult patients with considerable ventilator dyssynchrony and sedation requirements, such as COVID-19.

Extended Versus Short-Course Corticosteroid Taper Regimens in the Management of Chronic Obstructive Pulmonary Disease Exacerbations in Critically Ill Patients.

BACKGROUND: Previous literature has suggested that a short course of corticosteroids is similarly effective as an extended course for managing an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, there are limited data regarding the optimal corticosteroid regimen in critically ill patients and the dosing strategies remain highly variable in this population. METHODS: This retrospective cohort study evaluated patients with AECOPD admitted to the intensive care unit within a 2-year period. Patients were divided into short-course (≤5 days) or extended-course (>5 days) corticosteroid taper groups. The primary end point was treatment failure, defined as the need for intubation, reintubation, or noninvasive mechanical ventilation. Secondary end points included the duration of mechanical ventilation, hospital and intensive care unit length of stay, and adverse events. RESULTS: Of the 151 patients who met the inclusion criteria, 94 received an extended taper and 57 received a short taper. Treatment failure occurred in 3 patients, who were all in the extended taper group (P = .17). In a propensity score-matched cohort, the hospital length of stay was 7 days in the short taper group compared to 11 days in the extended taper group (P < .0001). No differences in adverse events were observed. CONCLUSION: A short-course corticosteroid taper in critically ill patients with AECOPD is associated with reduced hospital length of stay and decreased corticosteroid exposure without increased risk of treatment failure. A prospective randomized trial is warranted.

Cefepime versus carbapenems for the treatment of urinary tract infections caused by extended-spectrum ß-lactamase-producing enterobacteriaceae.

The aim of this study was to evaluate the effectiveness of cefepime compared with carbapenems for the management of urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae. This was a single-centre, retrospective study among patients with a documented ESBL-producing Enterobacteriaceae UTI between 1 July 2014 and 31 January 2017. Adult patients who received either cefepime or a carbapenem for symptomatic UTI were included in the analysis. The primary endpoint was clinical failure, defined by persistence of initial UTI symptoms that required escalation of therapy. Secondary endpoints included microbiological failure and relapse within 30 days. Of a total of 106 patients included in the study, 17 received cefepime and 89 received a carbapenem. None of the patients in either group experienced clinical or microbiological failure. Relapse occurred in six patients in the carbapenem group and none in the cefepime group. In conclusion, cefepime was comparable with carbapenems in the treatment of UTIs caused by ESBL-producing Enterobacteriaceae. Its use as a carbapenem-sparing agent for this indication should be further explored.

Clinical Outcomes in Patients With Gram-Negative Infections Treated With Optimized Dosing Cefepime Over Various Minimum Inhibitory Concentrations.

BACKGROUND: The Clinical and Laboratory Standards Institute (CLSI) revised cefepime interpretive criteria, introducing the susceptible dose-dependent category for Enterobacteriaceae with a minimum inhibitory concentration (MIC) of 4 to 8 µg/mL in 2014. Limited clinical data support these new categories. This study compares outcomes of patients treated with standard and high-dose cefepime across various MICs. METHODS: We retrospectively reviewed cases of pneumonia or bacteremia caused by gram-negative organisms treated with adequate doses of cefepime for ≥48 hours. Outcomes were compared for MICs of ≤2 (low), 4 (medium), and 8 µg/mL (high). The primary end point was clinical failure, the secondary end point was microbiological failure. RESULTS: Ninety cases met the inclusion criteria: 46, 25, and 19 patients with low, medium, or high MIC, respectively. Multivariate logistic regression revealed that the medium (odds ratio [OR]: 9.13, P < .01) and high (OR: 6.79, P = .01) MIC groups had increased clinical failure. CONCLUSION: Cefepime therapy, even at CLSI-recommended doses, had an increased risk of clinical failure for gram-negative pathogens with MICs of 4 or 8 µg/mL. This finding suggests that higher dosing regimens (2 g every 8 hours or 1 g every 6 hours) may be necessary to treat serious gram-negative infections with elevated MICs.

Combination Therapy With Vancomycin and Ceftaroline for Refractory Methicillin-resistant Staphylococcus aureus Bacteremia: A Case Series.

PURPOSE: Although vancomycin has been the mainstay of therapy for methicillin-resistant Staphylococcus aureus (MRSA) infections, its effectiveness has been challenged. Combination therapy may be used for patients with persistent MRSA bacteremia refractory to initial therapy. Studies have reported in vitro synergy between vancomycin and ceftaroline; however, clinical experience with this therapy is limited. Here, we report our experience with 5 cases of vancomycin-refractory MRSA bacteremia treated with the combination of vancomycin and ceftaroline. METHODS: Between January 2014 and August 2016, 5 patients were identified who received vancomycin and ceftaroline combination therapy due to persistent bacteremia or deterioration of their clinical status on vancomycin alone (despite a vancomycin MIC within the susceptible range). FINDINGS: Five patients presented with MRSA bacteremia secondary to endocarditis (n = 2), epidural abscess (n = 2), or left iliopsoas abscess (n = 1). Four of the 5 patients experienced microbiologic cure, and 1 patient transitioned to palliative care. IMPLICATIONS: This case series serves to describe additional clinical experience with vancomycin and ceftaroline combination therapy. This combination may be considered when vancomycin monotherapy does not lead to microbiological and/or clinical improvement in patients with metastatic MRSA bacteremia. Additional studies are warranted to further define its role in salvage therapy for persistent MRSA bacteremia.

Refractory Toxic Shock-Like Syndrome from Streptococcus dysgalactiae ssp. equisimilis and Intravenous Immunoglobulin as Salvage Therapy: A Case Series.

Infections from Streptococcus dysgalactiae ssp. equisimilis (SDSE) can cause a wide variety of infections, ranging from mild cellulitis to invasive disease, such as endocarditis and streptococcal toxic shock-like syndrome (TSLS). Despite prompt and appropriate antibiotics, mortality rates associated with shock have remained exceedingly high, prompting the need for adjunctive therapy. IVIG has been proposed as a possible adjunct, given its ability to neutralize a wide variety of superantigens and modulate a dysregulated inflammatory response. We present the first reported cases of successful IVIG therapy for reversing shock in the treatment of SDSE TSLS.

Efficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone.

STUDY OBJECTIVE: To assess the efficacy of intravenous chlorothiazide in patients with acute decompensated heart failure (ADHF) who were determined to be loop diuretic resistant and refractory to metolazone. DESIGN: Retrospective cohort study with patients serving as their own controls. SETTING: Large, academic, tertiary care hospital. PATIENTS: Forty-five patients with ADHF who had an inadequate response to high-dose loop diuretics and then received at least one dose of oral metolazone 5 mg or greater (metolazone index dose) followed by at least one dose of intravenous chlorothiazide 500 mg (chlorothiazide index dose) if the response to metolazone was considered inadequate, according to the institutional protocol, between February 4, 2013, and February 28, 2015, were included. If multiple doses of metolazone were administered, the last dose given before the chlorothiazide index dose was considered the index dose; the metolazone index dose had to have been administered more than 2 hours before the chlorothiazide index dose. MEASUREMENTS AND MAIN RESULTS: Data for a total of 90 diuretic doses (45 metolazone, 45 chlorothiazide) were included in the analysis. The median dose of loop diuretic in intravenous furosemide equivalents given over the 24-hour period before the metolazone index dose was 400 mg. The average length of stay was 34.7 days, and in-hospital mortality was 35.6% (16/45 patients). The primary end point of a net-negative urine output of 500 ml or greater during the 12 hours after the index dose occurred in 42.2% (19/45 patients) and 35.5% (16/45 patients) for the chlorothiazide and metolazone doses, respectively (p=0.581). The median 12-hour urine output following administration of metolazone was 810 ml (interquartile range [IQR] 866 ml) versus 1075 ml (IQR 940 ml) following administration of chlorothiazide (p=0.363). Compared with metolazone, the chlorothiazide doses did not result in an increase in urine output of at least 500 ml during the 12 hours following the dose relative to the 12 hours before the dose (31.1% vs 22.2%, p=0.754). No significant difference in achievement of net-negative urine output of 500 ml or greater during the 12 hours following the chlorothiazide or metolazone dose was noted (42.2% for chlorothiazide vs 35.5% for metolazone, p=0.581). CONCLUSION: The addition of intravenous chlorothiazide did not result in improved diuresis in patients with ADHF determined to be refractory to loop diuretics and adjunctive oral metolazone.

Cefepime free minimum concentration to minimum inhibitory concentration (fCmin/MIC) ratio predicts clinical failure in patients with Gram-negative bacterial pneumonia.

Cefepime is an antibiotic commonly used in nosocomial infections. The objective of this study was to elucidate the relationship between cefepime exposure and clinical outcome in patients with Gram-negative bacterial pneumonia. A previously published population pharmacokinetic model of cefepime was validated in 12 adult patients with normal renal function by measuring plasma concentrations at steady-state. Additionally, clinical outcomes for 33 patients with Gram-negative bacterial pneumonia who received cefepime monotherapy were determined. The free minimum concentration (fCmin) to MIC ratio for each patient was determined by conditioning the validated pharmacokinetic model using patient-specific creatinine clearance (CLCr), dosing regimen and cefepime MIC of the organism isolated, and was subsequently correlated with clinical failure. Classification and regression tree (CART) analysis was used to determine the most significant drug exposure breakpoint. Mean±S.D. CLCr and cefepime Cmin in the 12 patients were 87.5±21.2mL/min and 6.2±3.8mg/L, respectively. In comparison, the Cmin predicted by the pharmacokinetic model was 5.8mg/L using a CLCr of 90mL/min. MICs of organisms ranged from 0.5mg/L to 8mg/L. Percent time free drug above MIC of 100% was achieved in 32/33 patients, but 12 patients experienced clinical failure. CART analysis determined patients with an fCmin/MIC≥2.1 had a significantly lower risk of clinical failure (OR=0.11, 95% CI 0.02-0.67; P=0.017). The fCmin/MIC ratio is a useful predictor of clinical failure in Gram-negative bacterial pneumonia. The clinical utility of fCmin/MIC in therapeutic drug monitoring should be further explored.

Nitroglycerin administration during cardiac arrest caused by coronary vasospasm secondary to misoprostol.

There have been no reports of successful resuscitation using nitroglycerin (NTG) for cardiac arrest due to definitive coronary vasospasm. A 42-year-old female was brought to the Emergency Department in ventricular fibrillation after being found collapsed with the consumption of misoprostol. NTG, a potent coronary arterial dilator, not typically used in the management of cardiac arrest, was administered after 27 min of resuscitation efforts following advanced cardiac life support. NTG aided in the return of spontaneous circulation during a ventricular fibrillation cardiac arrest in the setting of prostaglandin use. .

Pain, agitation, delirium, and neuromuscular blockade: a review of basic pharmacology, assessment, and monitoring.

Agitation, pain, and delirium are focal points for targeted pharmacologic therapy in the intensive care unit. Understanding how to treat these essential entities necessitates fundamental understanding of the pharmacology of sedation, analgesia, and antipsychotics. Monitoring the effectiveness of these medications is crucial to optimize therapeutic outcomes and minimize untoward effects. Agents used in the management of agitation include drugs that target γ-aminobutyric acid A such as benzodiazepines and propofol and those with other targets such as dexmedetomidine and ketamine. Analgesia in the intensive care unit is controlled primarily using intravenous opioids, which differ on the basis of their potencies and pharmacokinetics. The management of delirium involves preventing its occurrence, removing potential causes, and pharmacotherapy with antipsychotics. Finally, the introduction of paralysis with the use neuromuscular blockers is often necessary in critically ill patients in various situations. In addition to understanding pharmacologic principles associated with the treatment of agitation, pain, and delirium, familiarization with the plethora of assessment tools used to guide therapy in these critically ill patients is mandated. This review focuses on the pharmacology of therapeutic agents used for sedation, analgesia, delirium, and neuromuscular blockade. Significant focus is given to the various assessment tools often used in practice today.

Tacrolimus Pharmacokinetic and Pharmacogenomic Differences between Adults and Pediatric Solid Organ Transplant Recipients.

Tacrolimus is a calcineurin inhibitor immunosuppressant that has seen considerable use in both adult and pediatric solid organ transplant recipients. Though there is much pharmacokinetic data available for tacrolimus in the adult population, the literature available for children is limited. Furthermore, very little is known about the pharmacogenomic differences in the two patient groups. Based on what information is currently available, clinically significant differences may exist between the two populations in terms of absorption, distribution, metabolism and elimination. In addition, inherent physiological differences exist in the young child including: less effective plasma binding proteins, altered expression of intestinal P-glycoprotein, and increased expression of phase 1 metabolizing enzymes, therefore one would expect to see clinically significant differences when administering tacrolimus to a child. This paper examines available literature in an attempt to summarize the potential pharmacokinetic and pharmacogenomic variability that exists between the two populations.