Evaluation of the use of sitagliptin for insulin resistance in burn patients.

BACKGROUND: Following severe burn injury, patients undergo profound metabolic changes, including insulin resistance and hyperglycemia. Hyperglycemia has been linked to impaired wound healing, increased risk of skin graft loss, increased muscle catabolism, increased infections, and mortality. Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that improves glycemic control by slowing the inactivation of incretin hormones, increasing insulin synthesis and release from pancreatic beta cells and lowering glucagon secretion from pancreatic alpha cells. The objective of this study was to describe our institution's experience with using sitagliptin to help mitigate insulin resistance after burn injury. METHODS: This was a retrospective chart review that included 22 adult burn patients. Burn patients were prescribed sitagliptin regardless of their previous medical history of type 2 diabetes mellitus. Patients were included in this analysis if they were adults admitted for burn injury during a 13-month period and received at least 3 consecutive doses of sitagliptin. Patients were excluded if they did not have insulin use data 3 days pre- and 3 days post-sitagliptin initiation. The first day of sitagliptin initiation was considered day 0; data from day 0 were not included in either the pre- or post-sitagliptin analysis. RESULTS: In the 3 days prior to sitagliptin initiation, patients received a median of 114.3 units per day (IQR 49.1, 228) in an attempt to maintain a blood glucose goal of less than 180 mg/dL. In the 3 days after sitagliptin was started, exogenous insulin requirements significantly decreased to a median to 36.3 units per day (IQR 11.7, 95) (P=0.009). Seven patients were on insulin infusions at the time of sitagliptin initiation. After sitagliptin was started, it took a median of 3 days (IQR 2, 3.25) to be liberated from the insulin infusion. In terms of safety, there were two episodes of hypoglycemia (BG<70 mg/dL) after sitagliptin initiation, compared to three episodes prior to sitagliptin initiation (P=0.7). CONCLUSION: The addition of sitagliptin to burn patients' medication regimens significantly reduced insulin requirements over a 3-day period and allowed liberation from insulin drips.

Angiotensin II in Decompensated Cirrhosis Complicated by Septic Shock.

This case describes the first reported use of human-derived synthetic angiotensin II (Ang-2) in a patient with decompensated cirrhosis and septic shock. The patient presented in vasodilatory shock from Enterobacter cloacae bacteremia with a Sequential Organ Failure Assessment Score of 14 and a Model for End-Stage Liver Disease score of 36. This case is significant because liver failure was an exclusion criterion in the Angiotensin II for the Treatment of Vasodilatory Shock (ATHOS-3) trial, but the liver produces angiotensinogen, which is key precursor to Ang-2 in the renin-angiotensin-aldosterone system. Resuscitation with Ang-2 is a potentially beneficial medication when conventional vasopressors have failed to control mean arterial pressure in this population.

Outcomes among Patients Treated with Renal Replacement Therapy during Extracorporeal Membrane Oxygenation: A Single-Center Retrospective Study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are modalities used in critically ill patients suffering organ failure and metabolic derangements. Although the effects of CRRT have been extensively studied, the impact of simultaneous CRRT and ECMO is less well described. The purpose of this study is to evaluate the incidence and the impact of CRRT on outcomes of patients receiving ECMO. METHODS: A single center, retrospective chart review was conducted for patients receiving ECMO therapy over a 6-year period. Patients who underwent combined ECMO and CRRT were compared to those who underwent ECMO alone. Intergroup -statistical comparisons were performed using Wilcoxon/Kruskal-Wallis and chi-square tests. Logistic regression was performed to identify independent risk factors for mortality. RESULTS: The demographic and clinical data of 92 patients who underwent ECMO at our center were reviewed including primary diagnosis, indications for and mode of ECMO support, illness severity, oxygenation index, vasopressor requirement, and presence of acute kidney injury. In those patients that required ECMO with CRRT, we reviewed urine output prior to initiation, modality used, prescribed dose, net fluid balance after 72 h, requirement of renal replacement therapy (RRT) at discharge, and use of diuretics prior to RRT initiation. Our primary endpoint was survival to hospital discharge. During the study period, 48 patients required the combination of ECMO with CRRT. Twenty-nine of these patients survived to hospital discharge. Of the 29 survivors, 6 were dialysis dependent at hospital discharge. The mortality rate was 39.5% with combined ECMO/CRRT compared to 31.4% among those receiving ECMO alone (p = 0.074). Of those receiving combined therapy, nonsurvivors were more likely to have a significantly positive net fluid balance at 72 h (p = 0.001). A multivariate linear regression analysis showed net positive fluid balance and increased age were independently associated with mortality. CONCLUSIONS: Use of CRRT is prevalent among patients undergoing ECMO, with over 50% of our patient population receiving combination therapy. Fluid balance appears to be an important variable associated with outcomes in this cohort. Rates of renal recovery and overall survival were higher compared to previously published reports among those requiring combined ECMO/CRRT.

Infections in patients with burn injuries receiving extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal Membrane Oxygenation (ECMO) has only recently been described in patients with burn injuries. We report the incidence and type of infections in critically ill burn and non-burn patients receiving ECMO. METHODS: A retrospective chart review was performed on all patients at Brooke Army Medical Center who received ECMO between September 2012 and May 2018. RESULTS: 78 patients underwent ECMO. Approximately half were men with a median age of 34 years with a median time on ECMO of 237 h (IQR 121-391). Compared to patients without burns (n = 58), patients with burns (n = 20) had no difference in time on ECMO, but had more overall infections (86 vs. 31 per 1000 days, p = 0.0002), respiratory infections (40 vs. 15 per 1000 days, p = 0.01), skin and soft tissue infections (21 vs. 5 per 1000 days, p = 0.02) and fungal infections (35% vs 10%, p = 0.02). Twenty percent of bacterial burn infections were due to drug resistant organisms. CONCLUSION: This is the first study to describe the incidence of infection in burn injury patients who are undergoing ECMO. We observed an increase in infections in burn patients on ECMO compared to non-burn patients. ECMO remains a viable option for critically ill patients with burn injuries.

The Interplay of Nutrition, Physical Activity, Severity of Illness, and Mortality in Critically Ill Burn Patients: Is There a Connection?

The purpose of this project was to evaluate the relationships between nutrition, physical activity levels (PALs), severity of illness (SOI), and survival in critically ill burn patients. We conducted a retrospective evaluation of consecutively admitted adult patients who had an intensive care unit stay ≥8 days after ≥20% TBSA burns. Linear regression was used to assess the association between SOI (sequential organ failure assessment scores) and PALs as well as between SOI and nutritional intake. After univariate analysis comparing survivors and nonsurvivors, factors with P < .10 were analyzed with multiple logistic regression. Characteristics of the 45 included patients were: 42 ± 15 years old, 37 ± 17% TBSA burns, 22% mortality. Factors independently associated with survival were burn size (negatively) (P = .018), height (positively) (P = .006), highest PAL during the first eight intensive care unit days (positively) (P = .016), and kcal balance during the fifth through the eighth intensive care unit days (positively) (P = .012). Sequential organ failure assessment scores had a significant (P < .001) but weak association with nutrition intake (R2 = 0.05) and PALs (R2 = 0.25). Higher nutritional intake and activity were significantly associated with lower mortality in critically ill burn patients. Given the weak associations between both nutritional intake and PALs with SOI, the primary barrier in achieving nutrition and activity goals was not SOI. We recommend that physical rehabilitation and nutritional intake be optimized in an effort to improve outcomes in critically ill burn patients.

A Review of Adjunctive Therapies for Burn Injury Pain During the Opioid Crisis.

Opioids are the mainstay of pain management after burn injury. The United States currently faces an epidemic of opioid overuse and abuse, while simultaneously experiencing a nationwide shortage of intravenous narcotics. Adjunctive pain management therapies must be sought and utilized to reduce the use of opioids in burn care to prevent the long-term negative effects of these medications and to minimize the dependence on opioids for analgesia. The purpose of this review was to identify literature on adjunctive pain management therapies that have been demonstrated to reduce pain severity or opioid consumption in adult burn patients. Three databases were searched for prospective studies, randomized controlled trials, and systematic reviews that evaluated adjunctive pain management strategies published between 2008 and 2019 in adult burn patients. Forty-six studies were analyzed, including 24 randomized controlled trials, six crossover trials, and 10 systematic reviews. Various adjunctive pain management therapies showed statistically significant reduction in pain severity. Only one randomized controlled trial on music therapy for acute background pain showed a reduction in opioid use. One cohort study on hypnosis demonstrated reduced opioid use compared with historical controls. We recommend the development of individualized analgesic regimens with the incorporation of adjunctive therapies in order to improve burn pain management in the midst of an abuse crisis and concomitant national opioid shortage.

Management of calciphylaxis in a burn center: A case series and review of the literature.

Calciphylaxis is a rare, necrotizing skin disorder usually associated with kidney disease, but also caused by many other systemic illnesses. This disease is associated with mortality rates as high as 80% at 1year. We present the demographic and clinical data of nine patients with calciphylaxis treated at our burn center over a 10year period. We review the literature on the clinical presentation, pathophysiology, diagnosis and treatment of this rare disease. We propose that these patients be treated similar to patients with thermal burn injury; meaning intensive wound care, surgical management, critical care and physical therapy. Burn centers are uniquely capable of caring for these incredibly complex patients due to their experience in managing patients with extensive skin and soft tissue defects, wounds and diseases.

Revisiting extracorporeal membrane oxygenation for ARDS in burns: A case series and review of the literature.

INTRODUCTION: Recent reports on the use of extracorporeal membrane oxygenation (ECMO) in critically ill burn patients with Acute Respiratory Distress Syndrome (ARDS) recommended against the use of ECMO. The authors cited the high mortality rates associated with the use of ECMO in these patients with no appreciable benefit. Accumulating evidence from referral centers suggests improved survival in patients with ARDS receiving ECMO. We report our recent experience treating patients with severe ARDS with ECMO in a burn intensive care unit. METHODS: This is a case series of consecutive patients placed on ECMO at our burn center from the initiation of our program in September 2012 to September 2017. We included only adult patients who had been placed on ECMO with burn injury, TEN, or inhalation injury and severe ARDS. RESULTS: Fourteen patients with burn injury, inhalation injury or TEN were placed on ECMO from the initiation of the ECMO program to September 1st 2017. The average total body surface area burned in the 11 patients with burn injury was 27% (range 0.25-76%). The cause of ARDS in these patients included inhalation injury, airway trauma and bacterial pneumonia. Four patients had an inhalation injury and 1 patient had a grade 3 inhalation injury but no burn injury. In the majority of cases, prone positioning and use of neuromuscular blockade was also used in an attempt to improve oxygenation and patient synchrony with mechanical ventilation. The average time on ECMO was 276h (range 63-539h). Ten of the 14 patients survived to decanulation from ECMO (71%) and eight of 14 patients (57%) survived to hospital discharge. CONCLUSIONS: To our knowledge, this is the lowest mortality rate reported to date in burn patients with ARDS place on ECMO. ECMO is a viable therapy that can be utilized successfully as a rescue modality when conventional interventions are unsuccessful.

Update on Severe Burn Management for the Intensivist.

Thermal injury of humans causes arguably the most severe perturbations in physiology that can be experienced. These physiologic derangements start immediately and can persist in some form until months or even years after the burn wounds are healed. Burn shock, marked activation of the systemic inflammatory response, multiple-organ failure, infection, and wound failure are just a few of the insults that may require management by the intensivist. The purpose of this article is to review recent advances in the critical care management of thermally injured patients.

Methemoglobinemia in patients undergoing esophagogastroduodenoscopy: a randomized controlled trial.

BACKGROUND: Methemoglobinemia is a potentially life-threatening complication of local anesthetic sprays employed in upper endoscopy. There is limited information available on the incidence of this complication, and no prospective trial has ever undertaken to evaluate subclinical levels of methemoglobinemia. OBJECTIVE: To evaluate the incidence of subclinical methemoglobinemia in patients exposed to anesthetic spray. METHODS: Subjects were randomized to a "spray" or "no-spray" group. Subjects in the "spray" group received a 1-second benzocaine spray before upper endoscopy. All subjects in both groups were monitored with a noninvasive co-oximetry device capable of detecting methemoglobin levels in real time. RESULTS: 401 subjects were enrolled (209 in the study group, 192 in the control group); mean peak methemoglobin concentrations were 0.82% (CI 0.74-0.90%, SD 0.57%) and 0.80% (CI 0.73-0.86%, SD 0.46%) respectively. There was no statistically significant difference between the two groups (p = 0.69). Only 3 (1.4%) subjects in the study group and 2 (1%) subjects in the control group had a peak methemoglobin concentration >2%. CONCLUSIONS: In this randomized clinical trial, no significant elevation of methemoglobin concentration was observed in any subject. Final analysis failed to demonstrate any statistically significant difference between the two groups.

A bedside communication tool did not improve the alignment of a multidisciplinary team's goals for intensive care unit patients.

PURPOSE: Establishing well-understood daily patient care goals should improve healthcare team (HCT) communication, reduce errors, and improve patient outcomes. The purpose of this study was to test the hypothesis that implementation of a daily goals "Door Communication Card" (DCC) would improve goal alignment between members of the HCT. METHODS: As part of a process improvement project, HCT members listed their top care goals for a patient on a given day. After initial data collection, DCCs were placed on patients' doors. Anyone was allowed to write on the card, but the "official" daily goals were recorded during multidisciplinary rounds. One month after introduction of the DCC, HCT members were re-queried about their patients' care goals. Three reviewers independently compared goals and assessed their alignment before and after implementation of the DCC. We collected goals over a 4-month period and selected 5 random days before and after intervention for assessment. RESULTS: The goal alignment among HCT members was low before and did not improve after intervention (Attending-to-Nurse 55% vs 38%, P = .02; Attending-to-Resident 60% vs 54%, P = .43; Attending-to-Primary 35% vs 28%, P = .45; Nurse-to-Attending 52% vs 36%, P = .03; Nurse-to-Resident 55% vs 38%, P = .04; Nurse-to-Primary 37% vs 27%, P = .36; Resident-to-Attending 59% vs 54%, P = .4; Resident-to-Nurse 56% vs 40%, P = .05; Resident-to-Primary 36% vs 24%, P = .16; Primary-to-Attending 34% vs 42%, P = .44; Primary-to-Nurse 42% vs 35%, P = .6; Primary-to-Resident 32% vs 34%, P = .8). CONCLUSIONS: Alignment of daily patient care goals among HCT members is low overall and did not improve after implementing a DCC available to all team members. Further study to elucidate the mechanism by which daily goals forms improve patient care is required.