Opioids and Immunosuppression: Clinical Evidence, Mechanisms of Action, and Potential Therapies.

Background: In addition to the more well-known adverse effects of opioids, such as constipation, mounting evidence supports underlying immunosuppressive effects as well. Methods: In this study, we provide a narrative review of preclinical and clinical evidence of opioid suppression of the immune system as well as possible considerations for therapies. Results: In vitro and animal studies have shown clear effects of opioids on inflammatory cytokine expression, immune cell activity, and pathogen susceptibility. Observational data in humans have so far supported preclinical findings, with multiple reports of increased rates of infections in various settings of opioid use. However, the extent to which this risk is due to the impact of opioids on the immune system compared with other risk factors associated with opioid use remains uncertain. Considering the data showing immunosuppression and increased risk of infection with opioid use, measures are needed to mitigate this risk in patients who require ongoing treatment with opioids. In preclinical studies, administration of opioid receptor antagonists blocked the immunomodulatory effects of opioids. Conclusions: As selective antagonists of peripheral opioid receptors, peripherally acting mu-opioid receptor (MOR) antagonists may be able to protect against immune impairment while still allowing for opioid analgesia. Future research is warranted to further investigate the relationship between opioids and infection risk as well as the potential application of peripherally acting MOR antagonists to counteract these risks.

Evaluating the impact of motion artifact on noninvasive blood pressure devices.

Most automated sphygmomanometers use oscillometric algorithms. Motion, either patient-based or environmental, will affect the ability of a device to record an accurate blood pressure (BP). Members of the Association for the Advancement of Medical Instrumentation (AAMI) Sphygmomanometer Committee have been studying this problem for more than a decade. The AAMI TIR44 was the first publication to address the challenges of motion tolerance. The concepts described in TIR44 have led to the development of a draft of ISO 81060-4, a new standard for testing devices for which the manufacturer wishes to claim motion tolerance. The current ISO 81060-2 addresses both stress testing and 24-hour ambulatory BP monitoring. Recent publications have reported on testing of devices in response to voluntary and involuntary patient motion. The ISO 81060-4 will address testing in the presence of patient transport by ground, fixed-wing, and rotary (helicopter) ambulances. The protocol will utilize noise profiles recorded under those three conditions. The profiles will be digitally stored on a library with free access. The proposed testing will be performed using patient simulators introducing the noise library files into known BP oscillometric envelopes. The specifications of the data capture and playback devices are specified, as is the evaluation statistical testing. The authors expect that the final draft will be published in 2020.

Inaccuracy of Urine Output Measurements due to Urinary Retention in Catheterized Patients in the Burn ICU.

Electronic urinary output monitors, intended to provide urine output information to guide fluid therapy during burn resuscitation, can be inaccurate because of airlocks causing urine retention in the drainage tube and bladder. In this study, the authors explore the effects of airlock formation on urine output measured using an electronic urinary output monitor connected to either a standard commercial drainage tubing system or a drainage tubing system with an automated airlock clearing mechanism. In a multicenter study in the burn intensive care unit, urine output was compared between 10 control patients with a standard commercial drainage tubing system and 10 test patients with a novel automated airlock clearing drainage tubing system. The comparison was focused on identifying the number and magnitude of surges in urinary output because of airlocks and associated periods of false oliguria. In the control group, 5 of 10 (50%) patients had drainage line flow impediments from 8 airlocks. In addition, control patients experienced six associated periods of false oliguria. Airlock surge volumes ranged from 50 to 329 ml, and false oliguria duration ranged from 39.4 to 185.2 minutes. In the test group, 0 of 10 (0%) patients had drainage line impediments from airlocks (P < .01), and hence, there were no periods of false oliguria. Airlocks and associated periods of false oliguria occur with standard commercial drainage tubing and are eliminated using an automated airlock clearing drainage tube. Electronic urinary output monitoring with self-clearing drainage has the potential to improve tracking of real-time urine output and decrease caregiver workload.

Vitamin C in Burn Resuscitation.

The inflammatory state after burn injury is characterized by an increase in capillary permeability that results in protein and fluid leakage into the interstitial space, increasing resuscitative requirements. Although the mechanisms underlying increased capillary permeability are complex, damage from reactive oxygen species plays a major role and has been successfully attenuated with antioxidant therapy in several disease processes. However, the utility of antioxidants in burn treatment remains unclear. Vitamin C is a promising antioxidant candidate that has been examined in burn resuscitation studies and shows efficacy in reducing the fluid requirements in the acute phase after burn injury.

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.

Five-Lumen Antibiotic-Impregnated Femoral Central Venous Catheters in Severely Burned Patients: An Investigation of Device Utility and Catheter-Related Bloodstream Infection Rates.

The objective of this study is to determine the catheter-related bloodstream infection (CRBSI) rate in a severely burned patient population, many of whom required prolonged use of central venous catheters (CVCs). Between January 2008 and June 2012, 151 patients underwent placement of 455 five-lumen minocycline/rifampin-impregnated CVCs. CRBSI was defined as at least one blood culture (>100,000 colonies) and one simultaneous roll-plate CVC tip culture (>15 colony forming units) positive for the same organism. Most patients had accidental burns (81.5%) with a mean TBSA of 50%. A mean of three catheters were inserted per patient (range, 1-25). CVCs were inserted in the femoral vein (91.2%), subclavian vein (5.3%), and internal jugular vein (3.3%). Mean overall catheter indwell time was 8 days (range, 0-39 days). The overall rate of CRBSI per 1000 catheter days was 11.2; patients with a TBSA >60% experienced significantly higher rates of CRBSI than patients with a TBSA ≤60% (16.2 vs 7.3, P = .01). CVCs placed through burned skin were four times more likely to be associated with CRBSI than CVCs placed through intact skin. The most common infectious organism was Acinetobacter baumannii. Deep venous thrombosis developed in eleven patients (7%). The overall rate of CRBSI was 11.2, consistent with published rates of CRBSI in burn patients. Thus, femoral placement of 5-lumen CVCs did not result in increased CRBSI rates. These data support the safety of femoral CVC placement in burn patients, contrary to the Centers for Disease Control recommendation to avoid femoral CVC insertion.

A retrospective review of clinical experience with daptomycin for a variety of wound types in a burn and wound care facility.

OBJECTIVE: Daptomycin is a novel antibiotic with activity against many Gram-positive organisms that has demonstrated efficacy in the management of skin and soft tissue infections (SSTIs). However, data regarding the use of daptomycin for the management of burn wound infections are lacking. We assessed the efficacy and safety of daptomycin in the treatment of complicated skin and soft tissue infections (cSSTIs), including burn wound infections. METHODS: We performed a retrospective review of patients receiving daptomycin for burn wound infections and other cSSTIs in a referral burn and wound treatment center. RESULTS: Our review revealed an overall success rate (microbiological cure + clinically improved) of 99.5%, with an overall success rate of 98.5% among burn patients, specifically. The overall success rate was 100% among patients in the three other diagnosis groups (cSSTIs, chronic wounds, and other infections). A success rate of 98% was noted among the subset of patients with wounds associated with bacteremia. CONCLUSIONS: Our study suggests that daptomycin is a safe and effective agent for the management of burn wound infections, although further study is warranted to confirm these results.

Treating necrotizing fasciitis with or without hyperbaric oxygen therapy.

There is not enough clinical data to support the benefit of adjuvant HBO2 therapy for necrotizing fasciitis (NF). We retrospectively reviewed our 67 NF cases to compare the outcomes of adjuvant HBO2 therapy versus non-HBO2 therapy. The overall outcome and morbidity criteria were compared between a group of 29 NF patients who received the adjuvant HBO2 and a group of the remaining 38 NF patients treated by only surgery and other standards of care. This study did not find any difference between the groups in average length of hospital stay, and their mortality. However, six (25%) of the non-HBO2 group patients required amputation of extremities compared to one of the HBO2 group (Fisher exact p = 0.09). Although the benefit of adjuvant HBO2 therapy remains controversial for NF, and the outcomes of this study are not statistically significant, there is a trend in clinical outcomes which shows that the therapy has the potential to reduce the number of amputation and salvage extremities. These findings necessitate multicenter, prospective, case control study to assess the possible benefit of adjuvant HBO2 therapy for NF.

Burns in mobile home fires--descriptive study at a regional burn center.

Death from fires and burns are the sixth most common cause of unintentional injury death in the United States. More than (3/4) of burn deaths occurring in the United States are in the home. Mobile home fires carry twice the death rate as other dwellings. The aim of the study was to describe the characteristics of deaths and injuries in mobile home fire admitted in a regional Burn Center and to identify possible risk factors. A cross-sectional retrospective study was carried out among all burn patients admitted to a regional Burn Center between January 2002 and December 2004 (3469 patients). The study included patients who suffered a burn injury from a mobile home fire. The demographic characteristics of the patients, location of mobile home, associated inhalation injury, source of fire, comorbidity of the victims, employment status, insurance status, family history of burns, and outcomes of the treatment were incorporated in a data collection record. There were 65 burn patients in mobile home fires admitted to the Burn Center during the studied period. The average age of the patients was 39 years (ranging from 2 to 81 years, SD=16.06), 77% were male, 67% were white, and 79% were the residents in the suburban areas of Georgia, South Carolina, North Carolina, and Florida. The average TBSA of burns was about 21% (ranging from 1 to 63%, SD=17.66), 63% of the patients had associated inhalation, three inhalation injury only, and 69% patients required ventilator support. The average length of stay per TBSA percentage of burn was 1.01 days (P=0.00), controlling for age, preexisting medical comorbidities, and inhalation injury. About 88% of the patients had preexisting medical comorbid conditions, 74% were smokers, 64% reported as alcoholic, and 72% had at least some form of health insurance coverage. In 40% of the cases, the cause of the fire was unknown, 31% were caused by accidental explosions, such as electric, gasoline, or kerosene appliances, and 29% were due to other causes. About 40% of burns took place between December and February. Among the studied cohorts, 32% were unemployed, 15% were disabled, and 14% did not have any information about their employment status. One in every four patients had a family history of a burn. Eight (12%) died in the hospital during treatment. There was a higher prevalence of inhalation injury and higher case fatality among the burn patients in mobile home fires compared with the statistics of the Burn Center. Observation showed a higher number of smokers and alcoholics among the burn patients. The main sources of fire were from home appliances. Fewer people had health insurance coverage than the national standard and more people suffered from some sort of chronic illness compared with the national morbidity data.

Purpura fulminans: a case series managed at a regional burn center.

Purpura fulminans (PF) is a protein C deficiency disease process with a high case fatality rate; however, overall incidence of the disease remains relatively very low. The similarity between skin necrosis secondary to PF and full-thickness skin burns provides the rationale for treating PF case in a burn center. In this case series we reviewed our experiences in managing PF and their associated favorable outcomes. Retrospective chart review of five PF cases managed between September 2004 and August 2006 at our Burn Center with 100% survival. Management of cases following the standard care of the Burn Center for a full-thickness burn included antibiotics, fluid resuscitation, surgical debridement with skin grafting, and activated protein C (Drotrecogin alfa) replacement. Two patients required amputations of extremities and all had surgical debridement. One required hemodialysis and two needed both hemodialysis and positive-pressure mechanical ventilator. No patient experienced any bleeding complications during or after surgery while receiving activated protein C. Early diagnosis and treatment at a burn center may reduce mortality and morbidity and loss of extremities in PF cases.

Clinical utility and economic impact of introducing a bowel management system.

PURPOSE: The primary objective of this study was to compare rates of urinary tract and soft tissue infections in critically ill burn patients before and following introduction of a Bowel Management System (BMS). We also analyzed the economic impact of the BMS as compared to reactive management of fecal soiling via cleansing and dressing changes. METHODS AND MATERIALS: A retrospective case-matched before-after study was completed. Critically ill burn patients using a BMS were matched with similar patients managed before introduction of the device based on gender, total body surface area burned, burn location, ventilation days, and hospital length of stay. RESULTS: Reductions in hospital-acquired urinary tract infections and skin and soft tissue infections were observed after introduction of the BMS. Despite its initial cost, it proved more cost effective than a reactive bowel management strategy based on cleansing and dressing changes when fecal soiling occurs. CONCLUSIONS: Proactive use of a bowel management device appears to reduce some infectious sequelae in a complicated burn care population and proved cost-effective for our facility.