Deepali Dixit

The role of tigecycline in the treatment of infections in light of the new black box warning

Tigecycline is an antibiotic with a broad spectrum of activity. Similar to tetracycline antibiotics, tigecycline exerts bacteriostatic activity. Earlier studies documented the safety and efficacy of tigecycline for complicated intra-abdominal and complicated skin and skin-structure infections, which led to its approval. Recent systematic reviews and meta-analyses have suggested increased risk of death in patients receiving tigecycline compared to other antibiotics. The Food and Drug Administration has warned clinicians about increased risk for death in patients who received tigecycline with certain severe infections and have issued a black box warning. The increased mortality risk with tigecycline is most apparent in patients treated for hospital-acquired pneumonia, particularly ventilator-associated pneumonia. The cause of excess deaths in these trials is uncertain, but it is likely that most deaths in patients with these severe infections were related to progression of the infection. Further experience with tigecycline for serious infections with drug-resistant pathogens is currently warranted.

Management of Acute Alcohol Withdrawal Syndrome in Critically Ill Patients.

Approximately 16–31% of patients in the intensive care unit (ICU) have an alcohol use disorder and are at risk for developing alcohol withdrawal syndrome (AWS). Patients admitted to the ICU with AWS have an increased hospital and ICU length of stay, longer duration of mechanical ventilation, higher costs, and increased mortality compared with those admitted without an alcohol‐related disorder. Despite the high prevalence of AWS among ICU patients, no guidelines for the recognition or management of AWS or delirium tremens in the critically ill currently exist, leading to tremendous variability in clinical practice. Goals of care should include immediate management of dehydration, nutritional deficits, and electrolyte derangements; relief of withdrawal symptoms; prevention of progression of symptoms; and treatment of comorbid illnesses. Symptom‐triggered treatment of AWS with γ‐aminobutyric acid receptor agonists is the cornerstone of therapy. Benzodiazepines (BZDs) are most studied and are often the preferred first‐line agents due to their efficacy and safety profile. However, controversy still exists as to who should receive treatment, how to administer BZDs, and which BZD to use. Although most patients with AWS respond to usual doses of BZDs, ICU clinicians are challenged with managing BZD‐resistant patients. Recent literature has shown that using an early multimodal approach to managing BZD‐resistant patients appears beneficial in rapidly improving symptoms. This review highlights the results of recent promising studies published between 2011 and 2015 evaluating adjunctive therapies for BZD‐resistant alcohol withdrawal such as antiepileptics, baclofen, dexmedetomidine, ethanol, ketamine, phenobarbital, propofol, and ketamine. We provide guidance on the places in therapy for select agents for management of critically ill patients in the presence of AWS.

Constipation in Elderly Patients with Noncancer Pain: Focus on Opioid-Induced Constipation

Constipation is a common and often debilitating condition in the elderly, which may be caused by underlying disease conditions, structural abnormalities in the bowel, and a variety of medications such as anticholinergics, antidepressants, and opiates. In this review, we focus on opioid-induced constipation (OIC), which is often underrecognized and undertreated in the elderly. When opioid therapy is initiated, healthcare providers are encouraged to evaluate risk factors for the development of constipation as part of a thorough patient history. To this end, the patient assessment should include the use of validated instruments, such as the Bristol Stool Scale and Bowel Function Index, to confirm the diagnosis and provide a basis for evaluating treatment outcomes. Healthcare providers should use a stepwise approach to the treatment of OIC in the elderly. Conventional laxatives are a first-line option and considered well tolerated with short-term use as needed; however, evidence is lacking to support their effectiveness in OIC. Moreover, because of the risk of adverse events and other considerations, such as chewing difficulties and swallowing disorders, conventional oral laxatives may be inappropriate for the treatment of OIC in the elderly. Thus, the availability of new pharmacologic agents such as the peripherally acting µ-opioid receptor antagonists methylnaltrexone and naloxegol, which target the underlying causes of OIC, and the secretagogue lubiprostone may provide more effective treatment options for elderly patients with OIC.

Acute exacerbations of chronic obstructive pulmonary disease: diagnosis, management, and prevention in critically ill patients.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is a substantial source of disability in the United States. Moderate‐to‐severe acute exacerbations of COPD (AECOPD) can progress to respiratory failure, necessitating ventilator assistance in patients in the intensive care unit (ICU). Patients in the ICU with AECOPD requiring ventilator support have higher morbidity and mortality rates as well as costs compared with hospitalized patients not in the ICU. The mainstay of management for patients with AECOPD in the ICU includes ventilator support (noninvasive or invasive), rapid‐acting inhaled bronchodilators, systemic corticosteroids, and antibiotics. However, evidence supporting these interventions for the treatment of AECOPD in critically ill patients admitted to the ICU is scant. Corticosteroids have gained widespread acceptance in the management of patients with AECOPD necessitating ventilator assistance, despite their lack of evaluation in clinical trials as well as controversies surrounding optimal dosage regimens and duration of treatment. Recent studies evaluating the safety and efficacy of corticosteroids have found that higher doses are associated with increased adverse effects, which therefore support lower dosing strategies, particularly for patients admitted to the ICU for COPD exacerbations. This review highlights recent findings from the current body of evidence on nonpharmacologic and pharmacologic treatment and prevention of AECOPD in critically ill patients. In addition, the administration of bronchodilators using novel delivery devices in the ventilated patient and the conflicting evidence surrounding antibiotic use in AECOPD in the critically ill is explored. Further clinical trials, however, are warranted to clarify the optimal pharmacotherapy management for AECOPD, particularly in critically ill patients admitted to the ICU.

Management of Hepatic Encephalopathy: A Primer

Objective: To review the management of hepatic encephalopathy (HE), including lifestyle modifying strategies and pharmacological interventions. Data Sources: A literature search of PubMed through March 2016 was conducted utilizing the keywords hepatic encephalopathy, ammonia, and cirrhosis. All published articles evaluating treatments for HE were considered. Study Selection and Data Extraction: Available English-language data from reviews, abstracts, presentations, and clinical trials of the treatment of HE in humans were reviewed; relevant clinical data were selected and included. Data Synthesis: HE is a prevalent complication of portal hypertension and cirrhosis that results in altered mental status and neuropsychiatric impairment. Although the pathogenesis has not been elucidated, numerous treatment options exist. This review will explore the role of dietary interventions and supplements, including use of zinc, acetyl-l-carnitine, and probiotics, in the management of HE. Additionally, the use of various ammonia-lowering agents will be evaluated. The nonabsorbable disaccharides represent first-line therapies for the management and prophylaxis of HE; rifaximin use has been demonstrated to be effective for both treatment and prophylaxis of HE symptoms, with use relegated to those patients who fail to respond to or tolerate the nonabsorbable disaccharides. In light of toxicities associated with the use of neomycin and metronidazole, recent guidelines recommend both as alternatives for the treatment of HE, with the use of vancomycin discouraged. Conclusion: Although numerous treatment options are available, management of HE remains a clinical challenge. Additional research is needed to explore the pathogenesis and better understand the role of pharmacotherapy in managing this condition.

Letter by Dixit and Thomas Regarding Article, "Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association".

Largely on the basis of the landmark Second Intensive Blood Pressure Reduction in Acute Cerebral Hemorrhage Trial (INTERACT-2),1 the updated American Stroke Association/American Heart Association Guidelines for the Management of Spontaneous Intracerebral Hemorrhage (ICH) now recommend a systolic blood pressure (SBP) goal of <140 mm Hg in ICH patients who have no contraindications to SBP lowering.2 However, in contrast to the European Stroke Organization guidelines for ICH,3 the American Stroke Association/American Heart Association guidelines do not clearly state …

Stevens-Johnson Syndrome Associated With Chlordiazepoxide

Objective: To report a case of chlordiazepoxide-associated Stevens-Johnson syndrome (SJS). Case Summary: This case provides insight into a serious adverse drug reaction secondary to a drug not commonly associated with SJS. A 29-year-old female presented with a 4-day history of rash and pruritus. The rash started on her arms and spread all over her body. The patient was started on chlordiazepoxide 3½ weeks ago. On examination, there were multiple, raised, round erythematous lesions in various stages of healing. Skin erosions were noted on her lips and buccal mucosa. However, the rash did not involve the conjunctiva, inner ears, or genitalia. The patient was discharged home with a follow-up appointment with dermatology and instructions to discontinue chlordiazepoxide. Two days after her initial presentation, the patient’s rash spread to her eyes and genitalia. A painful, white film developed on her tongue, and she was unable to tolerate oral intake. She was emergently sent back to hospital and transferred to a Burn Unit. The biopsy report revealed full-thickness necrotizing keratinocytes in the epidermis consistent with SJS. Discussion: To our knowledge, there is only one other case report of chlordiazepoxide-associated SJS. Chlordiazepoxide is thought to be the cause of this patient’s biopsy-confirmed SJS and overall presentation. SJS is a rare but serious condition that is usually a result of drug exposure. Conclusions: The close temporal relationship between chlordiazepoxide initiation and onset of SJS provides a convincing theory as to the etiology of SJS in our patient.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units

Background: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013. Objective: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs). Methods: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation. The primary outcomes included adherence to 4 guideline recommendations: treatment of pain before sedation, use of nonnarcotic analgesic medications, use of nonbenzodiazepine sedative medications, and use of goal-directed sedation. Results: Of 138 patients evaluated, 50% had a primary medical diagnosis (as opposed to surgical, cardiac, or neurological diagnosis), and the median Sequential Organ Failure Assessment (SOFA) score was 7. Pain was treated prior to administration of sedatives in 55.4% of subjects, with fentanyl being the primary analgesic used. In addition, 19% received no analgesia, and 11.5% received nonopioid analgesia. Sedative agents were administered to 87 subjects (48 nonbenzodiazepine and 39 benzodiazepine). Of those receiving benzodiazepines, 22 received intermittent bolus regimens and 16 received continuous infusions, of which 5 were for another indication besides sedation. Validated scales measuring the degree of sedation were completed at least once in 56 (81.6%) patients receiving sedatives. Conclusions: Current sedation practices suggest that integration of evidence-based PAD guidelines across New Jersey adult ICUs is inconsistent despite pharmacist involvement.

Topiramate-Related Hyperammonemia

Objective: To report a case of hyperammonemia associated with the interaction between topiramate and valproic acid. Case Summary: We present a patient case with topiramate-related hyperammonemia. The patient was on topiramate prior to admission and presented with an elevated ammonia level following 2 doses of valproic acid. The increased dosing frequency of valproic acid further exacerbated the hyperammonemia. On discontinuation of topiramate and the tapering of the dose of valproic acid the patient’s ammonia level returned to normal. Discussion: Valproic acid–induced hyperammonemic encephalopathy is well documented and there are several proposed mechanisms. The interaction between valproic acid and topiramate causing drug-induced hyperammonemia encephalopathy is documented in several case reports. The interaction is associated with the addition of topiramate to a patient’s medication regimen that previously included valproic acid. Topiramate also has several proposed mechanisms for predisposing patients for hyperammonemia. There are limited data on topiramate monotherapy or long-term use of topiramate use causing hyperammonemia-associated encephalopathy or enhancing hyperammonemia with the addition of valproic acid. Conclusions: This case supports topiramate-related hyperammonemia and the pharmacodynamic interaction with the co-administration of valproic acid.

Neuroleptic malignant syndrome associated with haloperidol use in critical care setting: should haloperidol still be considered the drug of choice for the management of delirium in the critical care setting?

A 48-year-old man was brought to the emergency department because of intoxication. The patient was in respiratory distress, subsequently intubated for airway protection. On hospital day 5, he was diagnosed with delirium. Haloperidol was initiated at 5 mg intravenous every 6 h and titrated up to a dose of 60 mg /day over 5 days. On hospital day 18, his temperature peaked to 107.1°F. Other symptoms included mental status change, muscular rigidity and autonomic dysfunction. Neuroleptic malignant syndrome (NMS) associated with haloperidol was suspected. No other causes for these symptoms were present. Concurrent medications were reviewed and ruled out for possible drug-induced fever. Haloperidol was discontinued and dantrolene and bromocriptine was initiated. The temperature decreased to 102.2°F within 3 h and other symptoms resolved overtime. The temporal relationship between the patients fever decline with the discontinuation of haloperidol, and improvement with dantrolene and bromocriptine, the diagnosis was believed to be haloperidol-induced NMS.