Association between colistin dose and development of nephrotoxicity

Colistin is an antibiotic used to treat infections caused by Gram-negative bacteria. However, this medication is associated with nephrotoxicity. Several studies have suggested a dose-dependent relationship between colistin and this adverse effect. For this reason, colistin is typically reserved for treatment of extensively drug-resistant (XDR) bacteria, such as Pseudomonas aeruginosa and Acinetobacter baumannii.

In their retrospective cohort study, Lee, Wi, Kwon, et al. investigated the relationship between colistin dose and nephrotoxicity in 329 patients, the majority of which were ICU patients, between 2010 and 2013. 43.5 percent of these patients experienced at least a two-fold increase in serum creatinine concentration during their treatment with colistin. These patients were significantly older than patients who did not develop nephrotoxicity. 39 percent of patients with nephrotoxicity did not recover. While total cumulative dose and daily dose based on actual body weight were similar between the two groups, colistin dosing based on ideal body weight was significantly higher among patients with nephrotoxicity.

These results are significant because they suggest that higher doses of colistin may increase patients’ risk for developing nephrotoxicity. Furthermore, because patients in both groups received colistin for 8 days, I am interested in learning more about the relationship between the duration of treatment with colistin and nephrotoxicity. Based on the abovementioned findings, I would expect a longer duration to be associated with a greater risk for nephrotoxicity. This study also demonstrates the need for further research into treatment options for extensively drug-resistant (XDR) bacteria due to colistin’s serious adverse effects.

Crit Care Med. 2015;43(6):1187-93.

The effect of dexamethasone on symptoms of posttraumatic stress disorder and depression after cardiac surgery and intensive care admission

Following cardiac surgery, patients are typically admitted to the intensive care unit (ICU) for a short period of time. Studies suggest that 14 to 25 percent of these patients develop posttraumatic stress disorder (PTSD) and 23 to 32 percent develop depression. Corticosteroids produced via the hypothalamus-pituitary-adrenal (HPA) axis bind to glucocorticoid and mineralocorticoid receptors and help patients adapt to changing environments. Therefore, it is thought that patients with reduced HPA axis activity may be less able to adapt to such changes.

Kok, Hillegers, Veldhuijzen, et al. studied the effect of dexamethasone on the prevention of PTSD and depression among 1,125 patients admitted to the ICU following cardiac surgery between April 2006 and November 2011. Dexamethasone is a synthetic glucocorticoid, which acts on glucocorticoid receptors (GR) to produce anti-inflammatory effects. Of the 1,125 patients enrolled in this study, 561 patients received 1 mg/kg dexamethasone intravenously. This dose was administered following the start of anesthesia and prior to cardiopulmonary bypass. The remaining 564 patients received placebo.

In their 1.5-year follow-up, the authors report similar numbers of patients with PTSD or depression between the treatment and control groups. Among patients who received dexamethasone, 52 patients and 69 patients developed PTSD or depression, respectively. In comparison, 66 patients who received placebo had PTSD and 78 had depression at the time of follow-up. Overall, these results suggest that intraoperative administration of 1 mg/kg dexamethasone has no effect on patients’ likelihood of developing PTSD or depression following ICU discharge. However, dexamethasone was found to have a positive effect on female patients, reducing the prevalence of these psychiatric conditions in this subgroup.

Although this article specifically discusses the development of PTSD and depression following cardiac surgery, it is also applicable to other surgical procedures that require patients be admitted to the ICU. Therefore, this problem effects many patients we will see in the future as pharmacists. By suggesting that dexamethasone is not effective for the prevention of psychiatric conditions in patients following ICU discharge, the authors also demonstrate the need for further research for a solution.

Crit Care Med. 2016;44(3):512-20.

Randomized, double-blind, placebo-controlled trial of thiamine as a metabolic resuscitator in septic shock: A pilot study

Thiamine is an essential cofactor for several enzymes involved in aerobic respiration. Several studies have demonstrated that thiamine deficiency is common among patients in septic shock. As a result, these patients have elevated lactate levels, acidemia, and hypotension. Donnino, Andersen, Chase, et al. studied the effect of thiamine administration on lactate levels in 88 patients with septic shock at two U.S. hospitals between 2010 and 2014.

Of the 88 patients enrolled, 43 received 200 mg thiamine in 50 mL 5% dextrose intravenously. The remaining 45 patients received placebo in a similar dextrose solution. Blood lactate levels were measured before administration of thiamine or placebo and also at 6, 12, and 24 hours following administration. 28 patients (15 in the thiamine group and 13 in the placebo group) were thiamine deficient at the onset of this study, suggesting a relationship between thiamine and septic shock.

The authors report significantly lower lactate levels at 24 hours following intravenous administration of 200 mg thiamine among patients with thiamine deficiencies. No such decrease was observed at 6 or 12 hours. Among patients with normal thiamine levels at onset, thiamine administration did not produce a significant difference in lactate levels. These results suggest that thiamine may decrease mortality among patients in septic shock with thiamine deficiency. However, thiamine may be less effective in patients with normal thiamine levels.

This study is important because it supports the relationship between thiamine deficiency and septic shock, while also demonstrating that the two do not always occur together. In fact, the majority of the 88 patients enrolled in this study had normal thiamine levels. The authors also demonstrate the need for further research into treatment options for septic shock. 

Crit Care Med. 2016;44(2):360-7.

Attitudes of research participants and the general public regarding disclosure of Alzheimer’s disease research results

Currently, results of Alzheimer’s disease (AD) research assessments, such as genetic testing and neuroimaging to determine brain amyloid levels, are not disclosed to patients for ethical reasons. However, several studies indicate interest in the disclosure of these results, despite the lack of a cure for AD.

In their study, Gooblar, Roe, Selsor, et al. examined the disclosure attitudes of 219 patients enrolled in a longitudinal aging study at the Knight Alzheimer’s Disease Research Center (KADRC). Of these patients, 60.7 percent were female, with a mean age of 75.6 years. All patients completed pre- and post-intervention surveys to assess their attitudes about the disclosure of their research results. Following completion of the pre-intervention survey, information about the benefits of disclosure, as well as the potential harms, were presented to 119 patients (education group). The remaining 100 patients (placebo group) were presented information about the KADRC. Both presentations were similar in length, taking approximately 20 to 30 minutes.

The authors report lower interest in disclosure among patients in the education group following intervention. This suggests that patients may believe that the harms associated with disclosure outweigh the benefits. However, within this group, patients with a family history of AD were more interested in disclosure. In comparison, there was no change in disclosure attitudes in the placebo group, as 96.9 percent of patients were interested before and after intervention.

This study is important because it examines an ethical issue involved with AD research. If it was determined that you were at a high risk for developing AD, would you want to be informed? If so, how would you use this information moving forward?

JAMA Neurol. 2015;72(12):1484-90.

Standardizing ICU management of pediatric traumatic brain injury is associated with improved outcomes at discharge

While considerable medical research has been done involving the treatment of traumatic brain injury (TBI) in adult patients, much less is known regarding treatment of TBI in pediatric patients, due to differences in CNS response. Guidelines for treatment in pediatric patients are summarized in the Brain Trauma Foundation guidelines, which were most recently updated in 2012. However, O’Lynnger et al. describe the need for further treatment standardization.

In their retrospective study of 128 pediatric patients with severe TBI from April 1, 2008 to May 31, 2014, the authors compared short-term outcomes before and after treatment was standardized on April 1, 2013. Goals of treatment for TBI include limiting secondary brain injury by increasing cerebral blood flow. Discharge disposition (either home, to rehabilitation, or death) and Glasgow Outcome Scale scores were used as measures of patient outcomes.

Following standardization, O’Lynnger et al. report favorable outcomes (i.e., discharge home) for 69 percent of patients, compared to 36 percent pre-protocol. In addition, this protocol reduced the number of patient deaths by 10 percent. Only one patient was discharged to rehabilitation during the study. Patients’ length of stay was similar before and after protocol implementation.

From these results, we can conclude that implementing standardized treatment for severe TBI in pediatric patients can improve short-term outcomes. This article is important because it highlights the need for additional medical research involving the treatment of TBI in pediatric patients. Also, by demonstrating the benefits of standardizing treatment for TBI, the authors urge further standardization in pediatric critical care units.

J Neurosurg Pediatr. 2016;17(1):19-26.

Medication Errors in Cardiopulmonary Arrest and Code-Related Situations

Medication errors that occur during medical emergencies are not well documented. However, following their systematic review of the literature, Flannery and Parli report that medication errors may occur more frequently than anticipated. According to the authors, these errors occur at all stages of treatment from prescribing to administration.

According to the literature, prescribing errors during code-related situations account for 10.7 to 46% of medication errors. While verbal prescribing is discouraged by many organizations, it is often necessary during emergency situations. The authors discuss ways, such as repeating the verbal order, to reduce the likelihood of medication errors during the verbal prescribing process. In addition, according to the literature, errors in medication administration during code-related situations account for 28 to 57.6% of medication errors.

The authors also explore medication errors that occur during preparation, as well as those that result from medication mislabeling and make additional recommendations to reduce such errors. For example, to reduce mislabeling errors, they recommend using two different sized syringes to draw up two different medications. What additional recommendations would you make to reduce medication errors during medical emergencies?

Am J Crit Care. 2016;25(1):12-20.

Hypothermia for Intracranial Hypertension after Traumatic Brain Injury

Hypothermia is often induced in patients following traumatic brain injuries to reduce intracranial pressure. However, according to Peter et al., therapeutic hypothermia plus standard care may not be as effective as standard care alone for treatment of traumatic brain injuries. Standard care includes several treatments, including but not limited to mechanical ventilation, sedation, elevating the head of the patients’ bed by 30 degrees, and administering intravenous fluids to maintain a mean blood pressure greater than or equal to 80 mmHg.

Their study included 387 patients receiving treatment for traumatic brain injuries from November 2009 until the trial was stopped due to safety concerns in October 2014. The Extended Glasgow Outcome Scale (GOS-E) was used to measure patients’ functional outcomes 6 months following injury. At the end of the trial period, Peter et al. report worse outcomes for patients in the hypothermia group. In addition, a favorable outcome, indicated by a higher GOS-E score, occurred more frequently following treatment with standard care alone.

One important takeaway from this article is the need for increased medical research into the management of traumatic brain injuries. This research is necessary due to the increased incidence of these injuries – a 21% increase in the past 5 years, according to Peter et al. Also, as a student pharmacist interested in both critical care and neurology, I enjoyed learning about the current treatment guidelines for traumatic brain injury, as well as the risks associated with therapeutic hypothermia.

N Engl J Med. 2015;373(25):2403-12.

Association of Seafood Consumption, Brain Mercury Level, and APOEe4 Status with Brain Neuropathology in Older Adults

In addition to long-chain n-3 fatty acids, which are necessary for normal brain function, seafood contains mercury, a neurotoxin. Morris et al. studied 286 autopsied brains to determine the relationship between seafood consumption, brain mercury and selenium levels, and brain neuropathologies. Mercury and selenium concentrations were measured in the inferior temporal and midfrontal lobes, as well as in the cerebellum. Selenium levels were of interest because selenium antagonizes mercury toxicity.

The authors determined that seafood consumption relates directly to brain mercury levels. However, they found no relationship between mercury levels and dementia-related pathologies. In fact, in individuals with the APOEe4 genotype, who have increased rates of lipid peroxidation, seafood consumption was associated with less severe plaques and tangles and a lower incidence of Alzheimer’s disease. On the other hand, increased brain selenium levels were associated with more severe tangles, which may contribute to Alzheimer’s disease.

Because brain levels of docosahexaenoic acid (DHA), a long-chain n-3 fatty acid, decrease as we age, the authors suggest that seafood consumption may be more beneficial for older adults or individuals with the APOEe4 genotype. Participants of this study died at a mean age of 89.9 years, and were mostly non-Hispanic white females. Therefore, further research must be done regarding the correlation between seafood consumption and brain neuropathologies in younger populations of various ethnicities.

JAMA. 2016;315(5):489-497.

Publication misrepresentation among neurosurgery residency applicants: an increasing problem

Although previous studies have demonstrated that applicants for surgical residencies have below average rates of publication misrepresentation, Kistka et al. report increased misrepresentation by neurosurgery residency applicants at Vanderbilt University Medical Center from 2006 to 2012. Compared to 47% of applicants in 2006, 97% of neurosurgery residency applicants at this program published peer-reviewed works. Furthermore, the average number of works per applicant increased significantly from 2006 to 2012.

While more applicants published a greater number of peer-reviewed works in 2012, the authors also report increased rates of publication misrepresentation between these years. In 2012, the most common types of publication misrepresentations included listing online only articles and abstracts in the section for peer-reviewed publications and false claims of publication. According to the authors, applicants from unranked medicals schools in the United States had 84% more publication misrepresentations compared to applicants from ranked schools.

Because it is extremely important for health professionals to be honest and trustworthy, so that we can foster open relationships with our patients, this article concerns me. I wonder if this trend of increasing publication misrepresentation can also be seen among other residency applicants, in particular pharmacy residency applicants.

J Neurosurg. 2016;124(1):193-98.