Comparison of Standard-Dose Versus High-Dose Dexmedetomidine in Extracorporeal Membrane Oxygenation.

BACKGROUND: Dexmedetomidine is commonly used to achieve light sedation in patients on extracorporeal membrane oxygenation (ECMO) despite minimal evidence. In vivo studies have shown dexmedetomidine sequestration in ECMO circuits, and higher doses may be used to overcome sequestration. OBJECTIVE: The purpose of this study was to compare safety and efficacy of dexmedetomidine at standard versus high doses in ECMO. METHODS: A retrospective analysis of adult ECMO patients was performed. Patients were compared as receiving either standard-dose (≤1.5 µg/kg/h) or high-dose (>1.5 µg/kg/h) dexmedetomidine. Safety outcomes included new onset bradycardia or hypotension. Efficacy was compared by the addition of concomitant sedative and analgesic agents. RESULTS: One hundred five patients were evaluated, with 20% of patients in the high-dose group. Comparing standard and high dosing, no significant differences were seen in primary safety outcomes including bradycardia (49% vs 38%, P = 0.46), hypotension (79% vs 71%, P = 0.56), or addition of vasopressors (75% vs 71%, P = 0.78). Need for concomitant analgesic agents and propofol was similar between groups. CONCLUSION AND RELEVANCE: This represents the first evaluation of use of high-dose dexmedetomidine in ECMO. Rates of dexmedetomidine higher than 1.5 µg/kg/h were commonly used in patients on ECMO, with similar rates of adverse effects and need for concomitant propofol and analgesic agents. While high-dose dexmedetomidine may be as safe as standard dose, no additional efficacy was found.

Adjusted vs Total Body Weight-Based Dosing of Sedation and Analgesia Used in the Intensive Care Unit.

Background: The purpose of this study was to evaluate if dosing fentanyl, dexmedetomidine, and propofol based on ideal or adjusted vs actual weight in patients would decrease overall opioid and sedative use. Methods: This was a retrospective chart review comparing adjusted vs actual weight-based dosing protocol of mechanically ventilated (MV) intensive care unit (ICU) adult patients who required fentanyl and either propofol or dexmedetomidine. Results: A total of 261 patients were included in which 101 patients were in the actual weight group and 160 patients were in the adjusted weight group. Total doses per MV day of fentanyl was 1042 ± 1060 µg in the actual weight group vs 901 ± 1025 µg in the adjusted weight group (P = .13). Total doses per MV day of midazolam was 20 ± 19 mg in the actual group vs 15 ± 19 mg adjusted group (P = .02). Average MV days was 8.2 vs 7.1 days, ICU length of stay was 10.6 vs 9.4 days, and self-extubation rates were 17.8% vs 4.4% in the actual group and adjusted group, respectively. Conclusion: Total midazolam doses per MV day were lower in the adjusted group. No significant change was seen in MV days, ICU length of stay, or self-extubation rates.

Change in Management of Status Epilepticus With the Addition of Neurointensivist-Led Neurocritical Care Team at a Rural Academic Medical Center.

Learning Objective: Status epilepticus (SE) is continuous clinical and/or electrographic seizures lasting 5 minutes or more without recovery and carries a high mortality. Medication management varies by institution, as well as administration, combination of antiepileptic drugs (AEDs), and dosing. Methods: Single-center retrospective review of medication management of SE patients admitted to West Virginia University Hospital before and after neurointensivist implemented guidelines. Patients admitted between January 2012 and June 2014 were grouped in the prior to neurointensivist group (pre-NI) and patients admitted between July 2014 and June 2016 were grouped in the postneurointensivist group (post-NI). Baseline demographics, hospital, intensive care unit (ICU), and ventilator length of stay were recorded. Medications reviewed included number of AEDs and maximum dose of lorazepam, phenytoin, levetiracetam, and lacosamide. Outcomes included number of continuous infusions of either midazolam or propofol at seizure suppression doses as well as pentobarbital, phenobarbital, or ketamine, and need for vasopressor use. Results: Of the 74 patients included, the pre-NI group (n = 40) utilized more AEDs (6 vs 4) compared with the post-NI group (n = 34). The pre-NI group had less midazolam continuous infusions meeting seizure suppression doses (8 vs 9), but higher average doses (49 vs 27 mg/h) compared with the post-NI group. More patients in the pre-NI group were on propofol seizure suppression doses (15 vs 10) and phenobarbital continuous infusions (11 vs 2) than the post-NI group. Patients had less vasopressor use in the post-NI group than the pre-NI group (11 vs 23). Frequency and dosing of lorazepam, phenytoin, levetiracetam, and lacosamide were similar between the 2 groups. Ventilator use, hospital, and ICU length of stay were also similar between groups. Discussion: Implementation of a neurointensivist and medication guidelines resulted in fewer AEDs and less vasopressor use in the management of SE. Midazolam use was slightly higher in the post-NI group but at lower doses overall.

Impact of Tissue Plasminogen Activator Dosing on Patients Weighing More Than 100 kg on 3-Month Outcomes in Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: The landmark National Institute of Neurological Disorders and Stroke (NINDS) tissue plasminogen activator (tPA) trial established the effectiveness and dosing of intravenous tPA for acute ischemic stroke (AIS) at .9 mg/kg with a maximum dose of 90 mg. Since the publication of the NINDS trial in 1995, there has been a drastic increase in the amount of obesity and the average weight of adults in the United States, which has caused an increase in the number of patients receiving 90 mg of alteplase for AIS. This retrospective trial was an attempt to see if reduced-dose tPA is as effective as full .9 mg/kg dosing. METHODS: We performed a single-center retrospective analysis to assess the dosing rate and 90-day outcomes comparing maximum dosage (90 mg) and standard dosage (.9 mg/kg) of tPA. RESULTS: A total of 301 patients were included in the analysis with 64 (21%) receiving less than .9 mg/kg dosing. The adjusted binary logistic regression model showed a statistically significant association toward a good outcome for increases in tPA dose rate (odds ratio = 1.7, P = .027) when compared against a poor outcome. Our analysis showed that patients receiving doses of alteplase closer to .9 mg/kg had a higher likelihood of a modified Rankin Scale score of 0-1 at 90 days. CONCLUSIONS: With the growth of obesity in the United States and the lack of data supporting dose capping of alteplase, it remains unclear if this dosing practice should continue to be accepted without question. Further studies are needed to assess optimum dosing practices particularly given the obesity epidemic.

Management of Complications of End-Stage Liver Disease in the Intensive Care Unit.

The management of critically ill patients with end-stage liver disease can be challenging due to the vulnerability of this population and the wide-ranging complications of the disease. This review proposes an approach based on the major organ systems affected, to provide a framework for managing the most common complications. Although considerable practice variation exists, a focus on the evidence behind the most common practices will ensure the development of the optimal skillset to appropriately manage this disease.

Spontaneous fungal peritonitis: a devastating complication of cirrhosis.

Spontaneous bacterial peritonitis is a well-known complication of cirrhosis; however, spontaneous fungal peritonitis (SFP) is less well-recognised and described. Our objective was to determine the clinical characteristics, treatment outcomes and factors associated with death among patients with SFP. We performed a retrospective cohort study using the primary outcome of all-cause mortality at 28 days. Twenty-five patients were included; Candida species were the causative pathogen in all cases. At the onset of SFP, patients were critically ill, median APACHE II and MELD scores were 22 and 30.3, respectively. The 28-day mortality rate was 56%; six patients died prior to culture positivity. Among the remaining patients, there were no differences in rates of death by treatment regimen (P = 0.55). APACHE II score at the onset of SFP was an independent predictor of death (OR = 1.46, 95% CI = 1.02-2.08, P = 0.04). In conclusion, SFP develops among critically ill patients with cirrhosis and is associated with high rates of death. Directed antifungal therapy did not improve patient outcomes. Future studies assessing the benefit of early or pre-emptive antifungal therapy are warranted.

An evaluation of intravenous vitamin k for warfarin reversal: are guideline recommendations being followed?

BACKGROUND: Vitamin K antagonists (eg, warfarin) remain the mainstay of anticoagulation therapy in the United States, with over 22 million prescriptions being filled annually. Unfortunately, warfarin therapy is difficult to manage and increases bleeding risk. The 2012 American College of Chest Physicians guidelines created a warfarin reversal algorithm that suggested the stringent use of intravenous vitamin K. OBJECTIVE: The purpose of this evaluation was to determine the rates of adherence with guideline recommendations in clinical practice. METHOD: A convenience sample of 3 months of intravenous vitamin K medication administration data (September to November 2013) was obtained to conduct a retrospective review. Patients with underlying hepatic dysfunction or lack of warfarin therapy were excluded. Vitamin K use was evaluated for consistency with the 2012 guidelines. RESULTS: A total of 364 patients were reviewed and 119 were included. Vitamin K utilization was consistent with guideline recommendations for a total of 30 (25.2%) patients. The most common site of active bleeding requiring reversal was head bleeds, consisting of 56.6% of bleeds. A single dose of 10 mg of vitamin K was the most frequently used dosing strategy. Fresh frozen plasma (73.3%) and four-factor prothrombin complex concentrate (36.7%) were the most commonly used factor products. CONCLUSION: This evaluation demonstrates that there is a difference between clinical judgment and guideline adherence. True adherence with the guidelines may not be necessary; however, there is room for improvement in both the appropriateness and safety of intravenous vitamin K use.

Continuous Intrathecal Medication Delivery With the IRRA flow Catheter: Pearls and Early Experience.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT medications delivered directly to the ventricle either by intermittent injection through an external ventricular drain (EVD) or by an Ommaya reservoir with a ventricular catheter. IT medication delivery through EVD has many drawbacks, including the necessary opening of a sterile system, delivery of medication in a bolus form, and requirements to clamp the EVD after medication delivery. Despite these setbacks, IT medications delivered through EVD have been used across a wide range of applications, including antibiotic delivery treatment of vasospasm with nicardipine and delivery of tissue plasminogen activator. METHODS: We used a newly developed active fluid exchange device to treat various severe conditions involved in the cerebral ventricles. Here, we present our treatment protocols and advice on the techniques related to successful active fluid exchange therapy. RESULTS: Seventy patients have been treated with our system with various conditions, including subarachnoid hemorrhage, intraventricular hemorrhage, ventriculitis, and cerebral abscess. Total complication rate was 14% with only 1 catheter occlusion and low rates of hemorrhage, infection, and spinal fluid leak. CONCLUSION: Current continuous IT medication dosages and protocols are based on reports and consensus statements evaluating intermittent instillation of medication boluses. The pharmacokinetics of continuous dosing and the therapeutic and safety profiles of the medications need to be studied in a prospective manner to evaluate the true optimal dosing standards. Furthermore, the ability to deliver continuous, sterile medications directly through an IT route will open new avenues of pharmacotherapy that were previously closed. This report serves as a basic guide for the safe and effective use of the IRRA flow active fluid exchange catheter to deliver IT medications.

Tocilizumab Versus Baricitinib for the Treatment of COVID-19 in Patients With Obesity.

Background: Tocilizumab and baricitinib have emerged as potential treatments for patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) following the findings of the Recovery Group and the results of the COV-BARRIER study. Unfortunately, there is a lack of guidance regarding the use of these agents in high-risk patients, such as those with obesity. Objective: To compare the outcomes of tocilizumab and baricitinib as potential treatments for obese patients infected with SARS-CoV-2. Methods: This was a multi-center retrospective analysis comparing outcomes of obese patients who received the standard of care plus tocilizumab or baricitinib for the treatment of SARS-CoV-2. Included patients had a BMI >30 kg/m2, needed ICU level care, and required non-invasive or invasive ventilatory support. Results: This study included 64 patients who received tocilizumab and 69 patients who received baricitinib. When examining the primary outcome, patients who received tocilizumab had a shorter duration of ventilatory support (10.0 vs 15.0 days, P = .016) than patients who received baricitinib. Our secondary outcome of in-hospital mortality was lower in the tocilizumab group as well (23.4% vs 53.6%, P < .001). Tocilizumab was also associated with a non-significant reduction in new positive blood cultures (13.0% vs 3.1%, P = .056) and new invasive fungal infection (7.3% vs 1.6%, P = .210). Conclusions: This retrospective review showed a reduced duration of ventilatory support in obese patients who received tocilizumab vs baricitinib. In the future, additional studies should be conducted to further examine and confirm these results.

Safety and efficacy of peripheral nerve blocks to treat refractory headaches after aneurysmal subarachnoid hemorrhage - A pilot observational study.

Objectives: Headache after aneurysmal subarachnoid hemorrhage (HASH) is common, severe, and often refractory to conventional treatments. Current treatment standards include medications including opioids, until the pain is mitigated. Peripheral nerve blocks (PNBs) may be an effective therapeutic option for HASH. We conducted a small before-and-after study of PNBs to determine safety, feasibility, and efficacy in treatment of HASH. Methods: We conducted a pilot before-and-after observational study and collected data for 5 patients in a retrospective control group and 5 patients in a prospective intervention PNB group over a 12-month period. All patients received a standard treatment of medications including acetaminophen, magnesium, gabapentin, dexamethasone and anti-spasmodics or anti-emetics as needed. Patients in the intervention group received bilateral greater occipital, lesser occipital, and supraorbital PNBs in addition to medications. The primary outcome was pain severity, measured by Numeric pain rating scale (NPRS). All patients were followed for 1 week following enrollment. Results: The mean ages in the PNB group and control group were 58.6 and 57.4, respectively. One patient in the control group developed radiographic vasospasm. Three patients in both groups had radiographic hydrocephalus and IVH, requiring external ventricular drain (EVD) placement. The PNB group had an average reduction in mean raw pain score of 2.76 (4.68, 1.92 p = 0.024), and relative pain score by 0.26 (0.48, 0.22 p = 0.026), compared to the control group. The reduction occurred immediately after PNB administration. Conclusion: PNB can be a safe, feasible and effective treatment modality for HASH. Further investigations with a larger sample size are warranted.

A Review of Push-Dose Vasopressors in the Peri-operative and Critical Care Setting.

During hospitalization, the risk of hypotension and associated sequelae remain important considerations for patient outcomes. The use of push-dose vasopressors (PDP) outside of the operating room has increased in recent years to combat the negative effects of hypotension. This narrative review evaluates the utility of PDP in its traditional perioperative setting as well as in areas of increasing use such as the emergency department and intensive care unit. Articles evaluating PDP highlight successful increases in blood pressure with all agents but differ in rates of adverse events and most lack direct comparison of PDP agents in regard to safety and efficacy. Agents utilized as PDP, including epinephrine, phenylephrine, norepinephrine, vasopressin, and ephedrine vary in mechanism of action, onset of action, and duration of action. These variations in pharmacology along with published literature may lead to differences in the preferred PDP for various clinical scenarios. Many adverse events associated with PDP have been due to dosing errors highlighting the importance of education surrounding the use of these agents. Additional research is necessary to further elucidate the risks and benefits of PDP in clinical practice, and to determine which PDP is truly preferred. Careful consideration should be given when determining the appropriateness of this administration method of vasopressors in various clinical scenarios.

Retrospective Assessment of the Use of Liposomal Bupivacaine in Lumbar Fusions in Immediate Postoperative Hospital Care.

BACKGROUND: Liposomal bupivacaine (LB) is approved by the U.S. Food and Drug Administration for administration into surgical sites for postsurgical analgesia. The liposomal formulation allows for sustained effects up to 72 hours. METHODS: A retrospective study assessed patients undergoing lumbar interbody surgery. Visual analog scale pain scores and amount of opioids consumed were recorded at 12-hour intervals for 72 hours postoperatively, as were patterns of discharge and hospital length of stay (LOS). RESULTS: A total of 122 patients (97 LB vs. 25 control group) were reviewed. Median LOS was shorter in the LB cohort compared with controls (1.94 vs. 3.08 days, respectively; P = 0.0043). When assessing the percentage of discharges between groups at 12-hour intervals, there were significantly more discharges in the LB cohort at 36-48 hours (P = 0.0226), and no differences elsewhere. There was a decrease in intravenous opioids consumed at 48-60 hours in the LB cohort compared with controls (P = 0.0494), a difference not detected at other time points or with oral or total opioids. Mean visual analog scale scores were significantly higher in the LB cohort compared with controls at 0-12 hours (5.2 vs. 3.9, respectively; P = 0.0079), but insignificantly different subsequently up to 72 hours. The LB cohort and controls were not significantly different in total amount of opioids consumed, overall pain scores, or regarding how the opioid amount consumed or pain scores changed over time. CONCLUSIONS: The use of LB in lumbar interbody fusion decreases patients' LOS but has little effect on reducing overall pain scores or opioid use in the 72-hour postoperative hospital period.

The effectiveness of intravenous vitamin K in correcting cirrhosis-associated coagulopathy.

OBJECTIVES: The goal of this study was to evaluate the effectiveness of intravenous (IV) vitamin K in cirrhosis. METHODS: This was a retrospective study of cirrhotic patients, not on anticoagulation, with administration of IV vitamin K and a baseline INR > 1.5. The primary outcome was the effectiveness of therapy defined by a 30% decrease in INR or a reduction in INR to an absolute value of ≤1.5. KEY FINDINGS: A total of 96 patients were included in the cohort. There was an average decrease in INR of 0.31; however, 60 patients (62.3%) failed to achieve at least a 10% decrease. Sixteen patients (16.7%) met the primary effectiveness endpoint. CONCLUSIONS: The use of IV vitamin K to correct coagulopathy of cirrhosis may not be beneficial.

Comparing Cost, Efficacy, and Safety of Intravenous and Topical Tranexamic Acid in Total Hip and Knee Arthroplasty.

We conducted a study to compare the cost, efficacy, and safety of intravenous (IV) tranexamic acid (TXA) and topical TXA in primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). We retrospectively reviewed the cases of 291 patients who received either IV TXA or topical TXA before and after surgery. Significant differences favored topical TXA in reducing the postoperative decrease in hemoglobin levels in THA (P = .031) and TKA (P = .015) and calculated blood loss in TKA (P = .019). The groups did not differ in transfusion requirements for either THA or TKA. Topical TXA cost significantly more than IV TXA (P ≤ .0001). The benefits of using topical TXA to reduce the perioperative decrease in hemoglobin levels come with increased cost.