Michael J. Cawley

Electrolyte disturbances associated with commonly prescribed medications in the intensive care unit.

Electrolyte imbalances are common in critically ill patients. Although multiple disease states typically encountered in the intensive care unit may be responsible for the development of electrolyte disorders, medications may contribute to these disturbances as well. Medications can interfere with the absorption of electrolytes, alter hormonal responses affecting homeostasis, as well as directly impact organ function responsible for maintaining electrolyte balance. The focus on this review is to identify commonly prescribed medications in the intensive care unit and potential electrolyte disturbances that may occur as a result of their use. This review will also discuss the postulated mechanisms associated with these drug-induced disorders. The specific drug-induced electrolyte disorders discussed in this review involve abnormalities in sodium, potassium, calcium, phosphate, and magnesium. Clinicians encountering electrolyte disturbances should be vigilant in monitoring the patients medications as a potential etiology. Insight into these drug-induced disorders should allow the clinician to provide optimal medical management for the critically ill patient, thus improving overall healthcare outcomes.

Potential risk factors associated with thrombocytopenia in a surgical intensive care unit

We conducted a retrospective chart review of 193 patients admitted during a 3-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with length of stay in a surgical-trauma intensive care unit (SICU) and mortality. All records were reviewed beginning 24 hours after admission. Patients were followed for the duration of SICU stay or until death. Data collected and analyzed as potential risk factors for thrombocytopenia were age, gender, admitting diagnosis, classification (trauma, surgical, medical), APACHE II score, medical history, all scheduled drugs with start and stop dates, select laboratory values, arterial or central line placement, and complications. Thrombocytopenia occurred in 25 (13%) patients. These patients were more likely (p<0.05) than those without thrombocytopenia to have the following potential risk factors: presence of a central or arterial line (76% vs 46%, p<0.025), nonsurgical diagnosis (60% vs 37%, p<0.05), diagnosis of sepsis (p<0.001), and administration of phenytoin (p<0.01), piperacillin (p<0.005), imipenem-cilastatin (p<0.001), and vancomycin (p<0.005). A longer SICU stay (mean 21 vs 4.5 days, p<0.05) and increased mortality (16% vs 4%, p<0.05) were significantly associated with thrombocytopenia. Cefazolin administration was significantly associated with nonthrombocytopenia (p<0.05). Factors not associated with thrombocytopenia were age, gender, and administration of histamine2-receptor antagonists, heparin, enoxaparin, penicillins, ceftazidime, ceftriaxone, chloramphenicol, and amphotericin B. A central or arterial line was the only factor associated with the development of thrombocytopenia in a multiple linear regression analysis (p=0.0003, multiple r=0.2580). Thrombocytopenia is not a common occurrence in the SICU, but is associated with a longer SICU stay and increased mortality.We conducted a retrospective chart review of 193 patients admitted during a 3‐month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with length of stay in a surgical‐trauma intensive care unit (SICU) and mortality. All records were reviewed beginning 24 hours after admission. Patients were followed for the duration of SICU stay or until death. Data collected and analyzed as potential risk factors for thrombocytopenia were age, gender, admitting diagnosis, classification (trauma, surgical, medical), APACHE II score, medical history, all scheduled drugs with start and stop dates, select laboratory values, arterial or central line placement, and complications. Thrombocytopenia occurred in 25 (13%) patients. These patients were more likely (p<0.05) than those without thrombocytopenia to have the following potential risk factors: presence of a central or arterial line (76% vs 46%, p<0.025), nonsurgical diagnosis (60% vs 37%, p<0.05), diagnosis of sepsis (p<0.001), and administration of phenytoin (p<0.01), piperacillin (p<0.005), imipenem‐cilastatin (p<0.001), and vancomycin (p<0.005). A longer SICU stay (mean 21 vs 4.5 days, p<0.05) and increased mortality (16% vs 4%, p<0.05) were significantly associated with thrombocytopenia. Cefazolin administration was significantly associated with nonthrombocytopenia (p<0.05). Factors not associated with thrombocytopenia were age, gender, and administration of histamine2‐receptor antagonists, heparin, enoxaparin, penicillins, ceftazidime, ceftriaxone, chloramphenicol, and amphotericin B. A central or arterial line was the only factor associated with the development of thrombocytopenia in a multiple linear regression analysis (p=0.0003, multiple r=0.2580). Thrombocytopenia is not a common occurrence in the SICU, but is associated with a longer SICU stay and increased mortality.

Trichosporon beigelii infection: experience in a regional burn center

Trichosporon beigelii is a fungus once thought to cause only superficial infections, but recently has been increasingly identified as an opportunistic systemic pathogen in immunocompromised patients. There have been very limited reports of this organism in the burn patient population. We describe the first report of pharmacological management of invasive T. beigelii with a combination of amphotericin B and high dose fluconazole in a burn patient. Antifungal susceptibility testing of T. beigelii determined a change in minimum inhibitory concentrations (MICs) of amphotericin B and a consistent resistance pattern with the use of flucytosine. This paper will review our experience with T. beigelii fungus in a regional burn treatment center and review the literature on other experiences in the burn population.

Nontraditional Dosing of Ampicillin-Sulbactam for Multidrug-Resistant Acinetobacter baumannii Meningitis

A 52‐year‐old man was admitted to a local hospital with headache, nausea, vomiting, dizziness, photophobia, and confusion after a sudden fall. Progressive changes in neurologic function were noted despite neurosurgical intervention and broad‐spectrum antimicrobial coverage. Cerebral spinal fluid (CSF) culture identified Acinetobacter baumannii that was resistant to traditionally recommended therapies of amikacin and imipenem‐cilastatin. The organism demonstrated minimum inhibitory concentrations of greater than 32 μg/ml and 8 μg/ml, respectively, for these two agents. Ampicillin 2 g‐sulbactam 1 g every 3 hours was administered based on history of therapeutic failure of traditional dosing in our thermal injury population. Repeat CSF cultures after 12 days of ampicillin‐sulbactam therapy were negative. After 35 days, the patients A. baumannii infection was completely resolved. The patient experienced no adverse drug events or toxicity with this high‐dosage regimen.

Levofloxacin-Induced Toxic Epidermal Necrolysis in an Elderly Patient

Stevens‐Johnson syndrome and toxic epidermal necrolysis (TEN) are mild‐to‐life‐threatening adverse reactions that have been described after exposure to fluoroquinolones. No published reports, however, exist of exfoliative disease after treatment with levofloxacin. A 78‐year‐old woman with many medical problems, including chronic obstructive pulmonary disease, was treated with parenteral levofloxacin for community‐acquired pneumonia. She was discharged with oral levofloxacin to complete an additional 3 days of treatment as an outpatient. Two days after completing this regimen, the patient developed a rash with blistering. The rash progressed to TEN in 7 days, and she was transferred to a burn treatment center. She was treated with fluid resuscitation, wound dressing, and antibiotics. Her condition improved, and she was discharged after 22 days. To our knowledge, this case is the first published report of levofloxacin‐induced TEN.

Retention of Advanced Cardiac Life Support Knowledge and Skills Following High-Fidelity Mannequin Simulation Training

Objective. To assess pharmacy students’ ability to retain advanced cardiac life support (ACLS) knowledge and skills within 120 days of previous high-fidelity mannequin simulation training. Design. Students were randomly assigned to rapid response teams of 5-6. Skills in ACLS and mannequin survival were compared between teams some members of which had simulation training 120 days earlier and teams who had not had previous training. Assessment. A checklist was used to record and assess performance in the simulations. Teams with previous simulation training (n=10) demonstrated numerical superiority to teams without previous training (n=12) for 6 out of 8 (75%) ACLS skills observed, including time calculating accurate vasopressor infusion rate (83 sec vs 113 sec; p=0.01). Mannequin survival was 37% higher for teams who had previous simulation training, but this result was not significant (70% vs 33%; p=0.20). Conclusion. Teams with students who had previous simulation training demonstrated numerical superiority in ACLS knowledge and skill retention within 120 days of previous training compared to those who had no previous training. Future studies are needed to add to the current evidence of pharmacy students’ and practicing pharmacists’ ACLS knowledge and skill retention.

Propofol withdrawal syndrome in an adult patient with thermal injury.

A 48‐year‐old man with a history of ethanol abuse and bipolar disease fell asleep while smoking in an intoxicated state. The patient received a 30% total body surface area burn involving his face and upper torso that resulted in an inhalation injury. Several attempts at weaning from mechanical ventilation failed due to his extreme agitation, which was unresponsive to benzodiazepines, opiates, and antipsychotic agents. Propofol therapy was begun in combination with valproic acid, fluoxetine, and risperidone to assist in the treatment of his severe agitation associated with the bipolar disease, inhibiting ventilatory weaning. Repeated attempts to discontinue propofol were associated with withdrawal symptoms such as severe agitation, tremors, tachycardia, tachypnea, and hyperpyrexia. His symptoms resolved only after each time the propofol infusion was restarted. The patient received propofol for 95 days for management of his agitation before dying from refractory septic shock and multiple organ failure.

Assessment of a pharmacist-driven point-of-care spirometry clinic within a primary care physicians office

Objective To assess value-added service of a pharmacist-driven point-of-care spirometry clinic to quantify respiratory disease abnormalities within a primary care physicians office Methods This retrospective, cohort study was an analysis of physician referred patients who attended our spirometry clinic during 2008-2010 due to pulmonary symptoms or disease. After spirometry testing, data was collected retrospectively to include patient demographics, spirometry results, and pulmonary pharmaceutical interventions. Abnormal spirometry was identified as an obstructive and/or restrictive defect. Results Sixty-five patients with a primary diagnosis of cough, shortness of breath, or diagnosis of asthma or chronic obstructive pulmonary disease were referred to the spirometry clinic for evaluation. A total of 51 (32 patients with normal spirometry, 19 abnormal spirometry) completed their scheduled appointment. Calculated lung age was lower in normal spirometry (58.1; SD=20 yrs) than abnormal spirometry (78.2; SD=7.5 yrs, p<0.001). Smoking pack years was also lower in normal spirometry (14.4; SD=10.7 yrs) than abnormal spirometry (32.7; SD=19.5 yrs, p=0.004). Resting oxygen saturation of the arterial blood (SaO2) was higher in normal spirometry than abnormal spirometry (98.1% vs 96.5%, p=0.016). Mean change in the forced expiratory volume in one second (FEV1) after administration of bronchodilator was greater in patients with abnormal spirometry compared with normal spirometry (10.9% vs 4.1%, p<0.001). Spirometry testing assisted in addition, discontinuation or altering pulmonary drug regimens in 41/51 patients (80%) and the need for further diagnostic testing or physician referral in 14/51 patients (27.4%). Conclusions Implementation of a pharmacist-driven spirometry clinic is a value-added service that can be integrated with other clinical pharmacy services within the ambulatory care setting. Further studies are needed to determine the role of pharmacists in performing spirometry testing and measuring performance outcomes of the pulmonary patient.

Emergence of resistance of vancomycin-resistant Enterococcus faecium in a thermal injury patient treated with quinupristin-dalfopristin and cultured epithelial autografts for wound closure.

Vancomycin-resistant Enterococcus faecium and faecalis (VRE) remains a major complication among critically ill patients. A 26-year-old patient with 65% total body surface area burns (TBSA) was infected with several E. faecium strains during his admission that were resistant to vancomycin. Because chloramphenicol was the standard treatment at this time, this drug was initiated until, the organism was identified as E. faecium and reported as susceptible to quinupristin-dalfopristin. Given these data, it was then decided to discontinue the chloramphenicol therapy. Quinupristin-dalfopristin therapy resulted in initial reduction of fever and white blood cell counts that continued over the next 5 days. However, on day 7 of quinupristin-dalfopristin therapy, a return of fever and elevation of the white blood cell count was noted and a repeated E. faecium blood culture demonstrated sudden resistance to quinupristin-dalfopristin (Bauer-Kirby zone size <14 mm). Chloramphenicol was restarted and the patient improved slowly over a period of 16 days. Our indigenous VRE had limited exposure to quinupristin-dalfopristin in the recent past; however, resistance emerged with the first commercial use of this agent in our burn treatment center. High-dose chloramphenicol treatment did not appear to impair engraftment of cultured epithelial autografts (CEA) in this patient.

Intravenous Linezolid Administered Orally: A Novel Desensitization Strategy

A 41‐year‐old woman with a history of myasthenia gravis was admitted to a local hospital because of severe muscle weakness, ptosis, shortness of breath, nausea and vomiting, and fever. Blood cultures revealed Enterococcus faecium resistant to several antimicrobial agents. The organism had minimum inhibitory concentrations above 16 μg/ml for vancomycin and above 2 μg/ml for quinupristin‐dalfopristin. In the absence of therapeutic alternatives, treatment with linezolid was required (minimum inhibitory concentration 1.5 μg/ml). The first dose of linezolid resulted in a hypersensitivity reaction consistent with an immunoglobulin E‐mediated response requiring medical intervention. Because of a lack of intravenous access and because of limited availability of the oral suspension from the manufacturer, a desensitization protocol was implemented in which the intravenous formulation of linezolid was given orally. The patient was successfully desensitized by using an escalating, 14‐dose procedure. We believe this is the first case in the English‐language literature to describe successful desensitization with the oral administration of intravenous linezolid in a patient with E. faecium bacteremia who was allergic to oxazolidinone.