Comparison of fluid resuscitation weight-based dosing strategies in obese patients with severe sepsis.

OBJECTIVE: This study aims to compare the composite outcome of progression to septic shock between 30 mL/kg/ideal body weight (IBW) versus 30 mL/kg/non-IBW fluid resuscitation dosing strategies in obese patients with severe sepsis. METHODS: We retrospectively evaluated obese patients admitted to an academic tertiary care center for the management of severe sepsis. Patients were included if they had a fluid bolus order placed using the sepsis order set between Oct 2018 and Sept 2019. The primary objective was the composite of progression to septic shock, defined as either persistent hypotension within 3 h after the conclusion of the 30 mL/kg fluid bolus administration or the initiation of vasopressor(s) within 6 h of the bolus administration. RESULTS: Of 72 included patients, 49 (68%) were resuscitated using an IBW-based and 23 (32%) using a non-IBW-based dosing strategy. There were similar rates of progression to septic shock in the IBW and non-IBW groups (18% vs. 26%; p = 0.54). Median ICU and hospital LOS in the IBW group versus non-IBW group were (0 [IQR 0] vs. 0 [IQR 0 to 4] days; p = 0.13) and (6 [IQR 3 to 10] vs. 8 [IQR 5 to 12] days; p = 0.07), respectively. In-hospital mortality rates were similar between the groups. CONCLUSIONS: Our study results suggest that in obese septic patients, fluid administration using an IBW-dosing strategy did not affect the progression to septic shock.

Ketamine for Acute Pain Management and Sedation.

TOPIC: Ketamine is beneficial in clinical settings ranging from procedural sedation to the treatment of chronic pain. This article describes the clinical benefits of ketamine for treatment of acute pain and for sedation of patients undergoing mechanical ventilation. CLINICAL RELEVANCE: Ketamine causes analgesic and amnestic effects by noncompetitive inhibition of the N-methyl-D-aspartate receptor and activation of the opioid µ and κ receptors. Unlike other sedatives, ketamine provides analgesia and amnesia without causing hypotension or respiratory depression. Several studies have elucidated the clinical benefits of ketamine. The use of ketamine has extended beyond critical care areas such as the operating room and intensive care units. Nurses must be familiar with optimal clinical scenarios, monitoring parameters, and contraindications of ketamine. PURPOSE: To highlight the clinical utility and pharmacological properties of ketamine through a literature review. Current studies of ketamine in acute pain and sedation management are summarized. CONTENT COVERED: This narrative review describes pharmacological properties, dosing strategies, adminis-tration considerations, and adverse effects of ketamine.

Comparison of Fluoroquinolone Versus Non-Fluoroquinolone Therapy for Inpatient Treatment of Chronic Obstructive Pulmonary Disease Exacerbations.

Background: While antimicrobial use in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) is reserved for more severe cases, the current evidence available comparing fluoroquinolones (FQs) to other classes in the inpatient setting are lacking. Objective: To compare the effectiveness of FQ therapy compared with non-FQs (NFQs) during acute COPD exacerbations in hospitalized patients. Methods: In this single-centered institutional review board-approved retrospective chart review, participants were included if they were at least 18 years of age and hospitalized for an acute exacerbation of COPD. Patients were stratified into FQ or NFQ groups based on the initial antimicrobial regimen administered. The primary outcome was the clinical resolution rate after antimicrobial therapy. Secondary outcomes included length of hospital stay, duration of antimicrobial therapy, 30-day readmission rates, and Clostridioides difficile infection rates. Results: A total of 375 patients were included (FQ = 201; NFQ = 174). The NFQ group had a higher rate of clinical resolution (84.5% vs 76.1%, P = .0435). In a multivariable regression analysis, the association between NFQ therapy and higher rates of clinical resolution remained significant (odds ratio = 2.31; 95% confidence interval = 1.3-4.10; P = .0043). The FQ group had a shorter length of stay (4 vs 5 days; P = .0022) and shorter inpatient antibiotic duration (4 vs 5 days; P = .0200). Rates of Clostridioides difficile infection and readmission were similar between groups. Conclusions: NFQ therapy may provide a higher rate of clinical resolution while avoiding exposure to FQ therapy and known adverse effects associated with FQ use.

The Intranasal Route as an Alternative Method of Medication Administration.

Intranasal drug administration is a less invasive method of drug delivery that is easily accessible for adult and pediatric patients. Medications administered by the intranasal route have efficacy comparable to intravenous administration and typically have superior efficacy to subcutaneous or intramuscular routes. The intranasal route is beneficial in emergent situations when the intravenous route is not available. The intranasal route is safe and effective in various indications, and therapeutic systemic concentrations of medication can be attained via this route. As the evidence for and comfort with intranasal administration continue to grow, guidance on correct technique, medications, and dosing is vital for appropriate use. This article reviews the process and practices of appropriate intranasal medication administration.

Initiative to reduce aztreonam use in patients with self-reported penicillin allergy: Effects on clinical outcomes and antibiotic prescribing patterns.

PURPOSE: Evaluation of the clinical impact of a pharmacist led-penicillin allergy assessment initiative to enhance antibiotic selection is reported. METHODS: A retrospective analysis was conducted on patients with a self-reported penicillin allergy (SRPA) at a 529-bed community teaching hospital and compared clinical response rate before and after implementation of a penicillin allergy assessment initiative, consisting of pharmacy staff education and pocket card development. Patients admitted with SRPA who received antibiotics with gram-negative coverage for at least 48 hours were included. The primary outcome was the clinical response rate of penicillin-allergic patients determined preimplementation and postimplementation of the initiative and was based upon improvement in signs and symptoms of infection. Secondary outcomes included antibiotics used, antibiotic durations, length of stay, survival rate, antibiotic discontinuation rate, and Clostridium difficile infection rate. RESULTS: A total of 280 patients were reviewed. Clinical response rate improved after implementation of the initiative (p = 0.047). There were significant differences in the type of antibiotics prescribed between the preimplementation group and the postimplementation group: increased cephalosporin use (p < 0.001), decreased aztreonam use (p = 0.017), and lower fluoroquinolone use (p = 0.008). Median length of stay (p = 0.943), in-hospital mortality rate (p = 0.173), and C. difficile infection rate (p = 0.426) were similar before and after implementation of the initiative. CONCLUSION: After implementation of an initiative to encourage the use of cephalosporins rather than aztreonam in patients with SRPA, the rate of clinical response and cephalosporin use increased and rates of exposure to aztreonam and fluoroquinolones decreased.

Comparison of Oral and Intravenous Tranexamic Acid for Prevention of Perioperative Blood Loss in Total Knee and Total Hip Arthroplasty.

BACKGROUND: Tranexamic acid (TA) is an antifibrinolytic agent that prevents perioperative blood loss in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). This benefit has been established with the intravenous (IV) dosage form, but there is limited evidence evaluating oral TA in this setting. OBJECTIVE: To compare the effect of oral versus IV TA on perioperative blood loss in those undergoing TKA or THA. METHODS: In this single-centered retrospective chart review, participants at least 18 years of age who received IV or oral TA from a single surgeon who performed their THA or TKA were included. The primary outcome evaluated hemoglobin (Hgb) reduction. Power analysis determined that 165 participants were required in each group to achieve 80% power, with a noninferiority margin of 0.3 mg/dL. RESULTS: Both study groups included 165 participants. Oral TA was noninferior to IV TA (Hgb difference = -0.12 g/dL [95% CI = -0.28 to 0.05; P = 0.0250]). A subgroup analysis of THA and TKA revealed that oral TA was noninferior to IV TA in THA (Hgb difference = 0.24 g/dL [95% CI = -0.17 to 0.5]), but oral TA failed to meet the noninferiority margin in the TKA subgroup (Hgb difference = -0.20 [95% CI = -0.38 to -0.02]). CONCLUSION: This study provides evidence that oral TA is a clinically effective and cost-efficient alternative to IV TA in the setting of THA and TKA.

Impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus surveillance protocol.

PURPOSE: Results of a study to evaluate the impact of a pharmacist-driven methicillin-resistant Staphylococcus aureus (MRSA) surveillance screening protocol are reported. METHODS: A retrospective single-center, quasi-experimental, pre-post cohort study was conducted to assess medication-use and clinical outcomes before and after implementation of a protocol allowing pharmacists to order nasal swabs and polymerase chain reaction (PCR) testing for MRSA in selected patients receiving vancomycin for pneumonia or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Negative assay results were used to guide de-escalation of vancomycin therapy. The primary outcome was vancomycin days of therapy (DOT). Secondary outcomes included hospital length of stay, the rate of vancomycin-associated acute kidney injury, and in-hospital mortality. RESULTS: A total of 300 patients were identified for inclusion in the preprotocol group (n = 150) or postprotocol group (n = 150) through medical records review. Compared with patients in the preprotocol group, those in the postprotocol group had a median 2.1-day reduction in vancomycin DOT (2.1 days versus 4.2 days, p < 0.0001). Protocol implementation was also associated with a decrease in the median number of vancomycin serum levels obtained per patient but did not have a significant impact on other secondary outcomes. CONCLUSION: Among patients with suspected or confirmed pneumonia or an AECOPD, the expansion of pharmacists' traditional scope of practice to include a surveillance protocol using a MRSA PCR nares assay to guide vancomycin de-escalation resulted in a reduction in vancomycin utilization without compromising clinical outcomes.

Disparities in hemodynamic resuscitation of the obese critically ill septic shock patient.

BACKGROUND: With a growing obesity epidemic, the approach to care of this patient remains controversial and in many circumstances different than the general population. Appropriate hemodynamic support, although still controversial, remains a cornerstone of septic shock therapy. Catecholamines are currently recommended by guidelines without a preferred dosing strategy. However, the use of weight-based (µg kg-1 min-1) or nonweight-based (µg/min) vasopressor drip rates may impact patient care in these populations. METHODS: A multicenter retrospective chart review was conducted. Patients receiving nonweight-based catecholamine infusions for septic shock were grouped into nonobese (n = 112) or obese (n = 196), and evaluated based on hemodynamic resuscitation. For the primary outcome, groups were analyzed for the requirement of a secondary hemodynamic support agent to obtain a goal mean arterial pressure of greater than or equal to 65 mm Hg. Secondary outcomes included an evaluation of time to a secondary hemodynamic support agent, time to hemodynamic stability (HDS), ability to obtain HDS at 24 hours, and death due to cardiovascular collapse. RESULTS: With the exception of weight and sex, baseline characteristics were similar among groups. Early resuscitative fluids were given at a lower weight based, but not total volume dose in the obese group (nonobese, 34.8 mL/kg vs obese, 22.4 mL/kg; P < .0001). The primary end point of addition of any secondary hemodynamic support agent was significantly greater in obese patients when adjusted for institution (nonobese, 19% vs obese, 27%; adjusted odds ratio, 0.42; 95% confidence interval, 0.23-0.77). Time to HDS was also prolonged (nonobese, 3.5 hours vs obese, 5.3 hours; P = .006). CONCLUSION: This study calls into question the adequacy of a nonweight-based approach to hemodynamic support of critically ill obese patients. This strategy seems to result in less aggressive, lower weight-based vasopressor and fluid doses, and more diverse approach than their nonobese counterparts.

Idarucizumab for Reversal of Dabigatran-Associated Bleeding: Misnomer or Miracle?

BACKGROUND: The development of novel oral anticoagulants (NOACs) has revolutionized oral anticoagulation. Rapid incorporation of NOACs into general practice has heightened the demand for directed reversal agents. Idarucizumab is a targeted reversal agent that is approved for the urgent reversal of the anticoagulant effects of dabigatran. While it is a welcome addition to reversal strategies of dabigatran, a number of clinical questions exist regarding its place in therapy. OBJECTIVE: We describe controversies regarding the use of idarucizumab therapy in patients with dabigatran-associated bleeding. DISCUSSION: Although existing clinical studies show a rapid reversal of coagulation assays, these studies did not describe a corresponding improvement in mortality or rapid cessation of hemorrhage. It is questionable how heavily clinicians can rely upon the use of the surrogate endpoints in clinical studies, such as ecarin clotting time and dilute thrombin time. Another issue is whether patients exhibiting re-elevation of coagulation assays would benefit from an additional dose of idarucizumab, because this has not been studied. It is currently unclear if blood products must be given in addition to idarucizumab can be used as monotherapy. CONCLUSIONS: The initial data suggest a definite role for idarucizumab in treatment of bleeding associated with dabigatran. As more clinical practice experience is gained with the agent and the remaining data on its use are released, clinicians can better guide the clinical use of idarucizumab. At present, there is currently not enough evidence for idarucizumab to be used as monotherapy.

The Effectiveness of Zolpidem for the Treatment of Disorders of Consciousness.

Approximately, five million people in the United States live with the residual effects of brain injury. The causes of acquired brain injury can be categorized as traumatic brain injury or non-traumatic brain injury. There are currently no treatments shown to consistently enhance recovery from disorders of consciousness (DOC). Sporadic recovery from DOC after the administration of various pharmacological agents has been described in several case reports. Increase in arousal after zolpidem administration is seen in patients with vegetative state or minimally conscious state for treatment of restlessness and disturbances of their sleep-wake cycle. The use of zolpidem could be reasonable in select patients with neurologic injury but promising integrity of brain structures, such as intact deep and superficial gray matter structures and white matter connections.

Acute hypokalemic periodic paralysis possibly precipitated by albuterol.

PURPOSE: An episode of acute hypokalemic paralysis associated with the use of inhaled albuterol is described. SUMMARY: A 34-year-old woman admitted to the emergency department reported the development of pain and diffuse paralysis of the extremities and torso shortly after using an albuterol inhaler. At age 18, she had been diagnosed with hyokalemic periodic paralysis (HPP), a disorder of muscle membrane excitability caused by serum potassium depletion that can lead to life-threatening neuromuscular and cardiovascular complications. After a 15-year period of episodically recurring HPP symptoms despite long-term acetazolamide use, she was switched to spironolactone therapy and had experienced no HPP exacerbations for about 1 year. On her arrival in the emergency department, the patient's serum potassium concentration was 1.8 meq/L and she was mildly tachycardic (heart rate of 125 beats/min). After careful supplementation to gradually increase the serum potassium concentration to 5.4 meq/L, the patient slowly regained movement and strength in her extremities. Application of the adverse drug reaction probability scale of Naranjo et al. to this case yielded a score of 3, indicating that albuterol was possibly the cause of the patient's HPP exacerbation. Beta-2-adrenergic agonists and several other medications can affect serum potassium levels; although the potential risks posed by the use of such drugs in patients with a history of HPP are unclear, cautious use in the context of known HPP is advised. CONCLUSION: A patient previously diagnosed with HPP experienced an exacerbation of HPP possibly induced by inhaled albuterol treatment.

Ventilator-associated pneumonia due to Shewanella putrefaciens.

PURPOSE: The first reported U.S. case of ventilator-associated pneumonia evidently caused by Shewanella putrefaciens is described. SUMMARY: A 39-year-old man with severe head trauma was found face down and unresponsive in a river after a watercraft accident. After being resuscitated and transferred to the intensive care unit, the patient received treatment for a subarachnoid hemorrhage and spinal injuries. The patient was also found to have decreased breath sounds bilaterally. On hospital day 7, bronchoalveolar lavage was performed due to acute febrile illness and thick pulmonary secretions. The patient was treated empirically with i.v. vancomycin and cefepime. The culture results suggested pneumonia due to methicillin-sensitive Staphylococcus aureus and colonization with Pseudomonas aeruginosa. The vancomycin and cefepime were replaced with nafcillin, after which the pneumonia resolved. The patient continued to be febrile, with leukocytosis on hospital day 14. A subsequent bronchoalveolar lavage culture performed that day revealed the presence of S. putrefaciens. According to the culture and susceptibility results, S. putrefaciens was resistant to ampicillin-sulbactam and exhibited sensitivity to cefepime, piperacillin, piperacillin-tazobactam, gentamicin, ciprofloxacin, levofloxacin, and meropenem. The patient received a 14-day course of cefepime, eliminating any further sign of the pathogen. Over the next two months, the patient's condition continued to improve, and he was eventually discharged to a rehabilitation facility. CONCLUSION: A 39-year-old man developed ventilator-associated pneumonia evidently caused by S. putrefaciens. The pneumonia resolved after treatment with cefepime.