Continuous Etomidate for the Management of Cushing's Syndrome Complicated by Pulmonary Nocardiosis.

Severe Cushing's syndrome is associated with significant complications including opportunistic infections. In the setting of infection, urgent reduction of circulating cortisol is warranted and commonly used oral medications have a slow onset of effect. Here we describe a 29-years old female who presented to an outside hospital with symptoms of untreated Cushing's syndrome on ketoconazole. Following identification of a pulmonary Nocardia spp infection, she was transferred for a higher level of care. Her initial serum ACTH and cortisol levels after transfer were 106pg/mL and 53.7mCg/dL respectively. Given the severity of her nocardiosis and lack of response to ketoconazole, the patient was placed in the ICU and started on a continuous etomidate infusion. Her serum cortisol rapidly decreased to 5.7mCg/dL. She was transitioned to metyarapone and the etomidate infusion was weaned to off. The etomidate infusion was well tolerated without adverse effects or need for an advanced airway. Following discontinuation of etomidate, she was found to have a pituitary microadenoma that was resected. The patient was discharged from the hospital on antibiotics for the management of her Nocardia spp infection. In patients with severe Cushing's syndrome, continuous etomidate may be safe and effective for patients who are unresponsive to other therapies.

Outcomes and adverse effects of extremely high dose insulin infusions in ICU patients.

PURPOSE: Describe the characteristics, hospital course, and outcomes of adult ICU patients receiving extremely high dose insulin infusions compared to those with lower insulin requirements. MATERIALS AND METHODS: Retrospective observational study of 128 adult ICU patients receiving IV insulin infusions at a large academic medical center. Extremely high dose insulin infusions were defined as maximum rate ≥ 35 units/h. The primary endpoint was rate of hypoglycemia (BG < 70 mg/dL) and time to glucose control. A post-hoc matching analysis was performed for baseline imbalances. RESULTS: Analysis included 32 patents with extremely high dose insulin infusions and 96 patients without, and most had a goal BG 100-150 mg/dL. Patients in the extreme group were more likely to have type 2 diabetes, a higher median hemoglobin A1c, preadmission insulin, be admitted for a medical reason, and receive inpatient steroids. The extreme group were more likely to experience hypoglycemia (<70 mg/dL, 63% v. 34%, p = 0.005), longer time to glucose control (19.8 h v. 5.7 h, p < 0.001) and higher mortality (34% v. 15%, p = 0.014). CONCLUSIONS: ICU patients with extremely high dose insulin infusions had more hypoglycemia and took longer to achieve glucose targets compared to those with lower requirements. An individualized approach may be required for appropriate management.

Use of Continuous Etomidate Infusion to Rapidly Correct Hypercortisolism in a Patient With Disseminated Nocardiosis.

Cushing's syndrome (CS) is an immunocompromised state characterized by impaired cellular and adaptive immunity due to hypercortisolism. This imbalance in the immune system leads to a high risk of opportunistic infections which can potentially prove fatal. In such patients, mortality can be reduced with early diagnosis and effective management of the underlying hypercortisolism. In this case report, we describe how prompt reduction of cortisol levels using a low dose continuous etomidate infusion was pivotal in effective treatment of an opportunistic infection, disseminated nocardiosis, in a 29-year-old female with Cushing's syndrome. We also discuss how treatment with antibiotics including empiric therapy with Imipenem and sulfamethoxazole/trimethoprim (SMX/TMP) and definite therapy as per susceptibility testing, with amikacin, SMX/TMP, and doxycycline helped to prevent adverse outcomes. Through this case, we aim to emphasize that infiltrates or cavitary lesions on the computed tomography (CT) scan of the chest in a patient with Cushing's syndrome should raise concern for nocardiosis, and prompt management with antibiotics should be initiated. Similarly, disseminated nocardiosis should always raise concern for possible immune deficiency states like Cushing's syndrome. Our case is unique in detailing the significance of using etomidate to acutely lower cortisol levels in a patient with endogenous CS and widespread invasive opportunistic infection. The pharmacology aspects of the Etomidate, in this case, have been published in the Journal of Pharmacy Practice and cited appropriately in this article.

Hemodynamic comparison of intravenous push diltiazem versus metoprolol for atrial fibrillation rate control.

OBJECTIVE: Intravenous push (IVP) diltiazem and metoprolol are commonly used for management of atrial fibrillation (AF) with rapid ventricular rate (RVR) in the emergency department (ED). This study's objective was to determine if there was a significant difference in blood pressure reduction between agents. METHODS: This was a single-center, retrospective study of adult patients initially treated with IVP diltiazem or metoprolol in the ED from 2008 to 2018. Primary endpoint was mean reduction in systolic blood pressure (SBP) from baseline to nadir during the study period. Study period was defined as time from first dose of IVP intervention to 30 min after last dose of IVP intervention or first dose of maintenance therapy, whichever came first. RESULTS: A total of 63 diltiazem patients and 45 metoprolol patients met eligibility criteria. Baseline characteristics were similar except for initial ventricular rate (VR) and home beta-blocker use. Median dose of initial intervention was 10 [10-20] mg and 5 [5-5] mg for diltiazem and metoprolol respectively. Mean SBP reduction was 18 ± 22 mmHg for diltiazem compared to 14 ± 15 mmHg for metoprolol (p = .33). Clinically relevant hypotension was similar between groups 14% vs. 16% (p = .86). Rate control was achieved in 35 (56%) of the diltiazem group and 16 (36%) of the metoprolol group (p = .04). CONCLUSION: IVP diltiazem and metoprolol caused similar SBP reduction and hypotension when used for initial management of AF with RVR in the ED. However, rate control was achieved more often with diltiazem.

Risk of Clostridium difficile infection in intensive care unit patients with sepsis exposed to metronidazole.

BACKGROUND: Antimicrobial agents used to treat Clostridium difficile infection (CDI), such as metronidazole and vancomycin, have been used during antibiotic treatment of other infections to try to prevent the development of CDI. We evaluated the hypothesis that intensive care unit (ICU) patients who receive metronidazole as part of an antibiotic treatment regimen for sepsis have a lower risk of subsequently developing CDI. METHODS: This was a nested case-control study in a cohort of ICU patients who received antibiotic therapy for sepsis. RESULTS: A total of 10 012 patients aged ≥ 18 years were admitted to the Cooper University Hospital medical/surgical ICU from 1/1/2003 to 12/31/2008. After applying inclusion criteria including having received antibiotic therapy for sepsis and subsequently having developed CDI, 67 cases were identified. The cases were matched for age, gender, date of ICU admission, and hospital length of stay to 67 controls that also received antibiotic therapy for sepsis but did not subsequently develop CDI. In the multivariate analysis, there was no association between metronidazole exposure and the risk of CDI (odds ratio (OR) = 0.57; p = 0.23). The only significant associations on multivariate analysis were antifungal therapy (OR = 0.30; p = 0.02) and aminoglycoside and/or colistin therapy (OR = 0.17; p = 0.02). CONCLUSIONS: No association was found between metronidazole use and subsequent CDI in ICU patients who received antibiotic therapy for sepsis.

Methylprednisolone sodium succinate-associated macroglossia in a critically ill patient.

Allergic hypersensitivity reactions are a rare adverse effect of corticosteroids. Previous reports have identified patients who developed symptoms of urticaria, dyspnea, hypotension, bronchospasm, and angioedema occurring within minutes to an hour after corticosteroid administration. A 35-year-old woman is described who developed an atypical reaction of isolated macroglossia after receiving intravenous methylprednisolone sodium succinate for myasthenic crisis. Macroglossia was identified on day 2 of therapy and worsened through day 5. On day 5, she was transitioned to prednisone 50 mg daily administered by feeding tube. Tongue swelling improved by day 7 and on day 10, the patient was extubated. The patient required reintubation due to stridor, but received a tracheostomy and was weaned off mechanical ventilation by day 15. The reaction was not confirmed with skin-prick tests, intradermal tests, or a drug rechallenge; however, she had previously received and tolerated all other drugs administered during this time. Due to the timing of administration and onset of symptoms, we feel this adverse drug reaction was likely due to administration of methylprednisolone. Applying the Naranjo adverse drug reaction probability scale to this case, a score of six was obtained, indicating a probable association between the administration of methylprednisolone and the development of macroglossia. As intravenous corticosteroids are often used in the treatment of allergic reactions, they may be overlooked as a cause of macroglossia and other allergic reactions; therefore, practitioners need to be aware of the possibility of this adverse effect secondary to corticosteroid administration. In the event of methylprednisolone sodium succinate-induced macroglossia, alternative nonesterified corticosteroids, such as dexamethasone or prednisone, should be considered if continuation of therapy is required.

Fidaxomicin for the treatment of Clostridium difficile infections.

OBJECTIVE: To evaluate the pharmacology, microbiology, safety, and efficacy of fidaxomicin for treatment of Clostridium difficile infections (CDI). DATA SOURCES: Literature was identified through Ovid MEDLINE (1948-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) using the search terms fidaxomicin, OPT-80, PAR-101, OP-118, difimicin, tiacumicin, lipiarmycin, Clostridium difficile, Clostridium difficile infection, Clostridium difficile-associated diarrhea, and cost. Drug monographs were retrieved from manufacturers' Web pages, and the Red Book component of Micromedex was used for cost information. STUDY SELECTION AND DATA EXTRACTION: All pertinent Phase 1, 2, and 3 studies published in English were included. DATA SYNTHESIS: Fidaxomicin is a macrocyclic compound bactericidal against C. difficile and inhibits toxin and spore production. It has poor oral absorption with high fecal concentrations. Available Phase 2 and 3 data with fidaxomicin 200 mg orally every 12 hours demonstrate similar effectiveness in treating CDI compared to oral vancomycin. Fidaxomicin was shown to have less frequency of recurrent infections. Adverse effects are uncommon and occur at similar rates as with oral vancomycin. The most frequently reported adverse effects are gastrointestinal, hematologic, and electrolyte disorders. Available data are lacking in several areas, including the efficacy and safety of fidaxomicin compared to established regimens for mild-to-moderate, life-threatening, and recurrent CDIs. The cost of a 10-day course of fidaxomicin is significantly more than that of metronidazole and vancomycin for treatment of mild-to-moderate CDI. CONCLUSIONS: Fidaxomicin appears to be an effective and safe alternative to oral vancomycin for treatment of mild-to-moderate and severe CDI. Data on its use compared to guideline-recommended therapies for mild-to-moderate and life-threatening CDI are needed. Further data assessing the cost-effectiveness of fidaxomicin are needed. Currently, it cannot be recommended over vancomycin for treatment of CDI. However, it may be considered for treatment of recurrent infections.

Computer-based simulation training to improve learning outcomes in mannequin-based simulation exercises.

OBJECTIVE: To assess the impact of computer-based simulation on the achievement of student learning outcomes during mannequin-based simulation. DESIGN: Participants were randomly assigned to rapid response teams of 5-6 students and then teams were randomly assigned to either a group that completed either computer-based or mannequin-based simulation cases first. In both simulations, students used their critical thinking skills and selected interventions independent of facilitator input. ASSESSMENT: A predetermined rubric was used to record and assess students' performance in the mannequin-based simulations. Feedback and student performance scores were generated by the software in the computer-based simulations. More of the teams in the group that completed the computer-based simulation before completing the mannequin-based simulation achieved the primary outcome for the exercise, which was survival of the simulated patient (41.2% vs. 5.6%). The majority of students (>90%) recommended the continuation of simulation exercises in the course. Students in both groups felt the computer-based simulation should be completed prior to the mannequin-based simulation. CONCLUSION: The use of computer-based simulation prior to mannequin-based simulation improved the achievement of learning goals and outcomes. In addition to improving participants' skills, completing the computer-based simulation first may improve participants' confidence during the more real-life setting achieved in the mannequin-based simulation.

Clinical and microbiologic outcomes in trauma patients treated for Stenotrophomonas maltophilia ventilator-associated pneumonia.

STUDY OBJECTIVES: To determine clinical and microbiologic plus clinical success rates in critically ill trauma patients who received treatment for Stenotrophomonas maltophilia ventilator-associated pneumonia (VAP). DESIGN: Retrospective medical record review. SETTING: Level I trauma intensive care unit of a large academic medical center. PATIENTS: A total of 101 patients who developed S. maltophilia VAP between January 1997 and December 2007. MEASUREMENTS AND MAIN RESULTS: Patients' baseline demographic and clinical characteristics, as well as characteristics of their VAP, were documented. The primary study outcome was the rate of clinical success in patients with S. maltophilia VAP; a secondary outcome was microbiologic plus clinical success rate in these patients. Standard definitions were employed to determine these outcomes related to VAP treatment. The study population had higher injury severity scores and a higher rate of traumatic brain injury than is typically observed in the study's intensive care unit. The median time to diagnosis of S. maltophilia VAP was 15 days (interquartile range 11-24 days). Stenotrophomonas maltophilia was the sole organism isolated in 34% of patients; the other patients had polymicrobial VAP. Despite inadequate empiric antibiotic therapy being administered to 97% of the patients, the overall clinical success rate was 87%. The microbiologic plus clinical success rate was 82%. The most common treatments for S. maltophilia VAP were trimethoprim-sulfamethoxazole (77 patients received monotherapy, 9 received combination therapy) and ciprofloxacin (6 patients received monotherapy, 8 received combination therapy); all-cause and VAP-related mortality rates were 13% and 7%, respectively. CONCLUSION: Critically ill trauma patients with S. maltophilia VAP responded well to therapy despite high rates of inadequate empiric antibiotic administration. Trimethoprim-sulfamethoxazole was the most common therapy, but clinical success rates did not differ significantly based on antibiotic selection. This study adds significantly to the available S. maltophilia VAP outcomes data.

Adjunctive aerosolized antibiotics for treatment of ventilator-associated pneumonia.

STUDY OBJECTIVE: To determine clinical and microbiologic success in patients receiving adjunctive aerosolized antibiotics for the treatment of ventilator-associated pneumonia (VAP). DESIGN: Retrospective medical record review. SETTING: Level I trauma intensive care unit of a large academic medical center. PATIENTS: Forty-nine patients (mean +/- SD age 42 +/- 19 yrs) who received aerosolized antibiotics for the treatment of a total of 60 episodes of VAP caused by Pseudomonas aeruginosa and/or Acinetobacter baumannii between January 2001 and July 2007. MEASUREMENTS AND MAIN RESULTS: Patients were identified by using an existing database of patients with documented VAP at the study center. To receive a diagnosis of VAP, patients had to have bacterial growth of 10(5) or more colony-forming units/ml from a bronchoscopic bronchoalveolar lavage and new or changing infiltrate on chest radiograph, plus at least two of the following: abnormal body temperature (> 38 degrees C or < 36 degrees C), abnormal white blood cell count (> 10 or < 4 x 10(3)/mm(3), or > 10% immature bands), or macroscopically purulent sputum. By reviewing patient data, we evaluated clinical and microbiologic success using standard definitions. The median (interquartile range) Injury Severity Score and admission Acute Physiology and Chronic Health Evaluation II score were 40 (29-45) and 17 (9-21), respectively. Pseudomonas aeruginosa, A. baumannii, or both were isolated in 45, 14, and 1 episode(s), respectively. Eighteen VAP episodes included additional bacteria. Aerosolized tobramycin, amikacin, and colistimethate were used in 44, 9, and 9 episodes, respectively. Systemic antibiotics were used in 59 (98%) of the 60 episodes. Clinical success was achieved in 36 (73%) of the 49 first episodes of VAP, 8 (73%) of 11 subsequent episodes, 17 (85%) of 20 episodes that were failing intravenous monotherapy, and 30 (79%) of 38 episodes with multidrug-resistant P. aeruginosa or A. baumannii. Microbiologic success was achieved in 29 (71%) of 41 evaluable episodes. Six patients died from VAP. CONCLUSION: Treatment with adjunctive aerosolized antibiotics was associated with a good response rate in critically ill trauma patients with VAP due to nonfermenting gram-negative bacilli. It is noteworthy that episodes of VAP that followed intravenous therapy failure and/or that were due to multidrug-resistant organisms responded well.

Evaluation of glycemic control following discontinuation of an intensive insulin protocol.

BACKGROUND: Intensive insulin protocols (IIPs) have been demonstrated to reduce morbidity and mortality in critically ill patients. Currently, there are no published studies evaluating glycemic control after discontinuation of an IIP. OBJECTIVE: The purpose of this study was to compare blood glucose (BG) control during an IIP and for 5 days following its discontinuation (follow-up period). METHODS: The study was a retrospective review of intensive care unit patients who received an IIP for >or=24 hours. Data were collected during the last 12 hours of the IIP and subsequent follow-up period. RESULTS: For all 65 included patients, the mean +/- standard deviation for BG on the IIP was 123 +/- 26 mg/dL versus 168 +/- 50 mg/dL following discontinuation of the IIP (P < 0.001). The median (interquartile range) insulin that was administered decreased from 40 (22-65) units on the IIP to 8 (0-18) units after the IIP was stopped (P < 0.001). The mean daily BG during the follow-up period was significantly higher than that during the IIP (P < 0.001). Additionally, an insulin requirement of >20 units during the last 12 hours of the IIP was identified as a risk factor for poor glycemic control during the follow-up period (odds ratio: 4.62; 95% confidence interval: 1.17-18.17). CONCLUSIONS: This study demonstrates a significant increase in BG following discontinuation of an IIP. Higher insulin requirements during the last 12 hours of an IIP were identified as an independent risk factor for poor glycemic control following the IIP. A standardized insulin transition protocol may help better control BG after discontinuation of an IIP.

Bivalirudin for patients with heparin-induced thrombocytopenia undergoing cardiovascular surgery.

OBJECTIVE: To evaluate the use of bivalirudin in patients with heparin-induced thrombocytopenia (HIT) undergoing cardiovascular surgery. DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-April 2008), International Pharmaceutical Abstracts (1960-April 2008), and Cochrane Databases (publications archived until April 2008) using the terms bivalirudin, heparin-induced thrombocytopenia, and cardiovascular surgery. STUDY SELECTION AND DATA EXTRACTION: Prospective and retrospective studies, case reports, and case series in adults were eligible for inclusion if bivalirudin had been used in a patient with known HIT undergoing any cardiovascular surgical procedure other than percutaneous coronary intervention. DATA SYNTHESIS: Two small, open-label, multicenter clinical trials were identified that evaluated treatment with bivalirudin in patients with HIT undergoing coronary artery bypass graft surgery. One looked at on-pump cardiopulmonary bypass (CPB), while the other looked at off-pump CPB. Procedural success was achieved at day 7 in 94% (n = 46) of patients in the on-pump CPB study and in 92% (n = 47) of patients in the off-pump CPB study. Dosing strategies varied between the 2 trials, with the on-pump study using a 1-mg/kg bivalirudin bolus followed by a 2.5-mg/kg/h infusion; the off-pump study used a 0.75-mg/kg bolus followed by a 1.75-mg/kg/h infusion. In addition, 10 case reports met the criteria to be included in the review and are summarized. In these cases, procedural success was reported using various bivalirudin doses in valve repair and replacement, right ventricular assist device implantation, and heart transplantation. CONCLUSIONS: Growing data demonstrate procedural success with bivalirudin in patients with HIT undergoing cardiovascular surgery. However, bivalirudin dosing and goal-activated clotting times varied between the studies and case reports. Bivalirudin represents a viable alternative to heparin in patients with HIT undergoing cardiovascular surgery; however, further trials are warranted to identify optimal dosing and monitoring parameters.