Amay Parikh

Myoclonus in renal failure: Two cases of gabapentin toxicity☆☆☆

Gabapentin, an AED approved for the adjunctive treatment of partial seizures with/without secondary generalization and for the treatment of postherpetic neuralgia, is frequently used off-label for the treatment of both psychiatric and pain disorders. Since gabapentin is cleared solely by renal excretion, dosing requires consideration of the patients renal function. Myoclonic activity may occur as a complication of gabapentin toxicity, especially with acute kidney injury or end-stage renal disease. We report 2 cases of myoclonic activity associated with gabapentin toxicity in the setting of renal disease which resolved with discontinuation of gabapentin and treatment with hemodialysis and peritoneal dialysis. As gabapentin has multiple indications and off-label uses, an understanding of myoclonus, neurotoxicity, and renal dosing is important to clinicians in multiple specialties.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddreys discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.

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.

Interhospital transfer handoff practices among US tertiary care centers: A descriptive survey

BACKGROUND Interhospital transfer is an understudied area within transitions of care. The process by which hospitals accept and transfer patients is not well described. National trends and best practices are unclear. OBJECTIVE To describe the demographics of large transfer centers, to identify common handoff practices, and to describe challenges and notable innovations involving the interhospital transfer handoff process. DESIGN AND PARTICIPANTS A convenience sample of 32 tertiary care centers in the United States was studied. Respondents were typically transfer center directors surveyed by phone. MAIN MEASURES Data regarding transfer center demographics, handoff communication practices, electronic infrastructure, and data sharing were obtained. RESULTS The median number of patients transferred each month per receiving institution was 700 (range, 250-2500); on average, 28% of these patients were transferred to an intensive care unit. Transfer protocols and practices varied by institution. Transfer center coordinators typically had a medical background (78%), and critical care-trained registered nurse was the most prevalent (38%). Common practices included: mandatory recorded 3-way physician-to-physician conversation (84%) and mandatory clinical status updates prior to patient arrival (81%). However, the timeline of clinical status updates was variable. Less frequent transfer practices included: electronic medical record (EMR) cross-talk availability and utilization (23%), real-time transfer center documentation accessibility in the EMR (32%), and referring center clinical documentation available prior to transport (29%). A number of innovative strategies to address challenges involving interhospital handoffs are reported. CONCLUSIONS Interhospital transfer practices vary widely amongst tertiary care centers. Practices that lead to improved patient handoffs and reduced medical errors need additional prospective evaluation. Journal of Hospital Medicine 2016;11:413-417.

Information handoff and outcomes of critically ill patients transferred between hospitals

PURPOSE Patients transferred between hospitals are at high risk of adverse events and mortality. This study aims to identify which components of the transfer handoff process are important predictors of adverse events and mortality. MATERIALS AND METHODS We conducted a retrospective, observational study of 335 consecutive patient transfers to 3 intensive care units at an academic tertiary referral center. We assessed the relationship between handoff documentation completeness and patient outcomes. The primary outcome was in-hospital mortality. Secondary outcomes included adverse events, duplication of labor, disposition error, and length of stay. RESULTS Transfer documentation was frequently absent with overall completeness of 58.3%. Adverse events occurred in 42% of patients within 24 hours of arrival, with an overall in-hospital mortality of 17.3%. Higher documentation completeness was associated with reduced in-hospital mortality (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.02 to 0.38; P = .002), reduced adverse events (coefficient, -2.08; 95% CI, -2.76 to -1.390; P < .001), and reduced duplication of labor (OR, 0.19; 95% CI, 0.04 to 0.88; P = .033) when controlling for severity of illness. CONCLUSIONS Documentation completeness is associated with improved outcomes and resource utilization in patients transferred between hospitals.

Acute kidney injury: taking aim at colistin

We appreciate the contribution of Rocco and colleagues [1], whose retrospective study in a recent issue of Critical Care evaluated risk factors for acute kidney injury (AKI) in patients receiving colistin methanesulfonate (CMS) or other nephrotoxic antimicrobials. The following key thoughts occurred to us after reviewing the study. We would like to address the criteria the authors used to qualify AKI. The authors note using RIFLE (Risk, Injury, and Failure; and Loss, and End-stage kidney disease) criteria to assess kidney injury, and note the degree of increase of serum creatinine from baseline in categorizing patients. However, the authors do not comment on urine output in these patients. Both urine output and serum creatinine are critical variables in recognizing kidney injury in a timely manner [2]. As noted, the literature on CMS pharmacokinetics is limited. A recent study investigating the pharmacokinetics of colistin noted that the maximum plasma concentration-to-minimum inhibitory concentration was much lower for Pseudomonas species than for other Gram-negative rods [3]. This implies that higher doses of CMS, and potentially more nephrotoxic doses, are required for treating Pseudomonas infections. Additionally, for those patients receiving continuous renal replacement therapy, the effective dose of antibiotic received may vary. It would be interesting to see what relationship, if any, exists between AKI and targeted bacteria species in critically ill patients on CMS. We appreciate the contribution of the authors to the literature on the prediction of AKI in critically ill patients receiving nephrotoxic antimicrobials. Further investigations into both the efficacy and potential harm of this antimicrobial are warranted.

The Case | Hyponatremia in a patient with obstructive jaundice

A 40-year-old man with a past medical history of autoimmune pancreatitis, lymphoplasmacytic sclerosing cholangitis, biliary stricture with stent placement, hyperlipidemia, and diabetes mellitus presented with fever for 2 days. Review of systems was negative for nausea, vomiting, poor oral intake, and diarrhea. He denied shortness of breath. Pertinent physical exam findings included fever, jaundice, icteric sclerae, moist oral mucosa, non-tender, non-distended abdomen, and absence of edema in lower extremities. No hepatomegaly was noted on exam. Laboratory tests revealed a serum sodium of 119 mEq/l, potassium of 3.3 mEq/l, chloride of 87 mEq/l, and a serum osmolality of 297 mOsm/kg. Total cholesterol was 2109 mg/dl. His lipid panel, however, demonstrated a low-density lipoprotein level of 68 mg/dl, high-density lipoprotein level of 36 mg/dl, and triglycerides of 299 mg/dl. Electrolytes on a repeat blood sample were checked simultaneously using the indirect ion-selective electrode (ISE) method and the direct ISE method. These results are depicted in the table below.

Regarding the benefits and harms of blood transfusion in septic patients.

Early Goal Directed Therapy has stressed the fact that quick, protocol-based intervention of sepsis improves outcomes. Growing evidence has questioned the utility of one such intervention, the transfusion of packed red blood cells (pRBCs), and we applaud Fuller et al.’s and others’ efforts to retrospectively analyze whether doing so is useful (1,2). Although a truly randomized study yielding essentially similar treatment arms is challenging to obtain in the critical care environment, we are concerned about the quality of the data in relation to the power to detect a change in goal mixed venous oxygen saturation (MvO2) or improved organ function. We would have preferred a similar Sequential Organ Failure Assessment (SOFA) score between the two groups, given the fact that a study endpoint was organ function. Additionally, although the Acute Physiology and Chronic Health Evaluation II score was similar between the two groups, this scoring system relies on a broad range of physiologic variables that are not necessarily related to a patient’s degree of critical illness or organ failure (unlike the SOFA score) (3,4). Given that the pRBC transfusion group was objectively much sicker than the non-pRBC group, it is likely that the pRBC group’s utilization of transfused products was relatively impaired and oxygen consumption was relatively increased. In addition, the pRBC group received more fluids, which can also influence pRBC utilization (5). These factors decrease the potential effect of pRBC transfusion onMvO2 in this group and are likely to significantly increase the sample size required to reach a reasonable power. Perhaps an additional study aiming for similarity in SOFA scores or other organ dysfunction severity markers (such as the Simplified Acute Physiology Score) would allow the authors to make a stronger assertion while maintaining the required sample size at an achievable number. Certainly, more study is needed. It has been said that our country does not have a blood donation problem, but rather has more of a blood overutiliza-

Selective decontamination: no oracle needed

We read with interest the study by Cuthbertson and colleagues [1] in a recent issue of Critical Care, and we appreciate their attempts to support studies regarding selective decontamination of the digestive tract (SDD). However, we have some concerns. The argument supporting a randomized controlled trial (RCT) for the evaluation of SDD is ambiguous. The Delphi method embraces ‘quasi-anonymity’, in which the researcher is aware of the responses of the participants [2]. The selection of experts is prone to bias, as participants were chosen on the basis of their inclusion among a particular group. Moreover, participants’ perception of SDD via a self-rated questionnaire is often misleading. Capacity to accurately reflect upon self-knowledge may be skewed, as we inflate the scope of our experience and understanding. The validity of a consensus is dubious, as dissidents are encouraged to alter their responses so as to better comport with the majority [2]. Knowing the time frame between rounds would be useful for readers. Using the Delphi technique and examining barriers to implementation may be novel, but the need for further evidence of effectiveness of SDD is not the limiting factor to widespread application. Given the 36 RCTs referenced, which consistently support its use, the benefits of SDD are proven, but rather the hindrance appears to be the lack of public attention or the concern for antibiotic resistance [3]. The digestive tract is particularly fragile in critically ill patients, and antibiotics have been shown to destabilize the gut microbiome, and this may increase developing resistance [4]. Notwithstanding these remarks, the authors highlight a promising intervention. Antibiotic resistance is an ongoing concern and should serve to prompt future studies.

Teaching central line placement: no clear window

We appreciate Maizel and colleagues addressing the teaching of ultrasound-guided central line placement to medical residents [1]; however, we have several comments. We feel that the success rates reported in this study are artificially high since most residents in 2014 are training with the use of ultrasound, and it is highly unlikely that the initial procedures being done by these senior residents (fourth and fifth year medical residents) were their first experience. In addition, by teaching the landmark technique second, the residents at that time are definitely experienced with the procedure of central line placement. The shorter procedure time noted for the landmark technique is likely related to the fact the practitioners are more experienced at this point and they did not need to set up the ultrasound machine. In addition, since procedure times were being measured, it would have been useful to separate out ‘difficult sticks’ [2]. It is anecdotally known that some patients have more difficult anatomy and require advanced maneuvers. Another possible variable that was not considered was the time of day of central line placement, since it has been established that central lines placed at night have higher complication rates than those placed during the day [3]. We feel that a better approach to answer the question of how to teach central line placement may be the concomitant approach: teach ultrasound-guided and landmark techniques at the same time to inexperienced practitioners, and then assess the success and complication rates.