Background: High tacrolimus intrapatient variability (tac IPV) is associated with poor outcomes in kidney transplantation, including rejection, donor-specific antibodies, and graft loss. A common cause of high tac IPV is related to patient nonadherence, but this is yet to be conclusively demonstrated. Methods:This was a longitudinal cohort study comprising adult kidney recipients, who received transplants between 2015 and 2017, with follow-ups through February 2020. The goal of this study was to identify the most common etiologies of tac levels outside the typical range, which lead to high tac IPV, and assess the etiologyspecific associations between high tac IPV and graft outcomes. Multivariate Cox regression was used to assess time-to-event analyses.Results: In total, 537 adult kidney recipients were included; 145 (27%) were identified as having a high tac IPV (.40%) 3-102 months post-transplant. Common etiologies of tac levels significantly outside the standard goal range (6-12 ng/mL) leading to high tac IPV included patient nonadherence (20%), infections (19%), tacrelated toxicities (17%), and undocumented issues (27%). In multivariable Cox modeling, those with high tac IPV because of nonadherence had a 3.5 times higher risk of late acute rejection (P = 0.019) and 2.2 times higher risk of late graft loss (P = 0.044). No other etiologies in the typical tac level range were significantly associated with either acute rejection or graft loss. Conclusions:Although high tac IPV has many causes, only high tac IPV caused by nonadherence is consistently associated with poor allograft outcomes.
Introduction Minimally invasive surgery has become standard of care across numerous subspecialties. However, burn surgery has lagged behind; as the mainstay of treatment still involves excision with a knife and a split thickness skin graft (STSG) with a painful donor site. Enzymatic debridement with bromelain and autologous skin cell spray (ASCS) have independently been STSG use and decrease the donor site size. Due to constraints with the time course of these products only being available via studies before one was FDA approved, these technologies have not been utilized together in the United States until recently. Little literature exists regarding their use in combination. The current study characterizes a series of patients who received “minimally invasive” skin grafts with enzymatic debridement and ASCS as proof of concept. Methods This was a retrospective study of a single academic burn center’s experience using bromelain and ASCS together. Data collection included demographics, injury characteristics, length of stay, complications, and measurements of donor sites, STSGs, and ASCS treatment. Donor site size:total area treated with ASCS and/or STSG was calculated. Length of stay (LOS) was qualitatively compared to expected using a factor of 1.1days:%TBSA, and O/E LOS ratio was calculated. Data was reported in medians with interquartile ranges. Patients with 1-30%TBSA qualified for the bromelain study and were treated according to protocol. Those deemed to have enough residual dermis were treated with ASCS, while 3rd degree areas received meshed split thickness skin patch grafts with ASCS overspray. Results Eleven patients were included in the study. Four patients received ASCS alone, while 7 patients received a meshed STSG on portions of their burn. Median burn size was 13% TBSA (IQR:5,20), while DPT+FT size was 9% TBSA (IQR:5,16). Patients had a median of 1067 sq cm (IQR:772,2183) of burn operatively treated with ASCS, and 351 sq cm (IQR:0,457) treated with meshed autograft. Donor site size (ASCS and STSG) was 225 sq cm (IQR:72,315), and ratio of donor site are to total treatment area was 0.0125 (IQR:0.01,0.32), suggesting an expansion of 80:1. Median LOS was 11 days (IQR:7,21), 0.84 days per %TBSA (IQR:0.5,1.16). Expected LOS was 14.3 days, with an O/E ratio of 0.77. Two patients developed infection; one required reoperation with STSG on half of his burned areas (5% TBSA). Conclusions Enzymatic debridement and ASCS can be used to treat burn injury with a “minimally invasive” approach. Donor sites were much smaller than expected had they been treated with a conventional meshed STSG on deep 2nd degree and 3rd degree areas. The data also suggests that length of stay was lower than expected. Further study is needed to determine which subsets of patients and burn wounds are optimal for this combination of technologies.
Introduction Existing literature supports bromelain enzymatic debridement as an early tool for selective escharectomy, resulting in fewer skin grafts after burn injury. Enzyme application is painful, so many centers use continuous infusions of narcotics, ketamine, and sedatives in the intensive care unit. The authors utilize oral ketamine in burn practice- as it is safe, can decrease the need for higher level of care, and be used without fasting. The purpose of this study is to evaluate whether oral ketamine can safely be utilized as an alternative to continuous infusions of medications for bromelain treatment. Methods This was a retrospective study of patients who received oral ketamine (for analgesia) and oral lorazepam (for anxiolysis and prevention of dysphoria) for bromelain-based selective enzymatic debridement application over a 6-month period. Data collected included patient demographics, burn characteristics, sedatives and analgesics administered, pain scores, adjunct medications, and vital signs. Presence of respiratory insufficiency (desaturations < 93%, need for bag-valve mask, or intubation), hypertensive urgency (SBP >180, DBP >110 w/out end organ dysfunction), dysphoric reactions, and uncontrolled pain were recorded. Oral ketamine (2-4 mg/kg) was given 30 minutes prior to the procedure. Patients were monitored per sedation guidelines and had capnography plus supplemental oxygen. Small PRN IV boluses of narcotics were given during the procedure, along with their baseline oral multimodals and narcotics. Pain was measured with the 1-10 verbal rating scale with minimal pain defined as < 4 or the patient clinically observed as sleeping. Patients were not made NPO for the procedure. Results Ten patients were included. Four patients (40%) had minimal pain during enzyme application, 3 (30%) patients slept through their procedure, and 3 (30%) patients reported 10/10 pain during treatment (2 had 10/10 pain before treatment). Five patients were treated on the floor, 7 were treated in the ICU. The median ketamine dose was 225 mg (IQR:177,250), or 3mg/kg (IQR:2.75,3). Additional oral and IV opioids received during the 8–14-hour interval was 21 morphine milligram equivalents (MEs). The median benzodiazepine dosing before and during enzymatic debridement was 1.4 lorazepam MEs. Three patients (30%) had hypertensive urgency, 2 (20%) of whom reported 10/10 pain, and all 3 received 10mg IV labetalol. No one had dysphoric reactions or respiratory insufficiency. Conclusions This preliminary study reveals oral ketamine administration is safe and effective for pain control during bromelain-based enzymatic debridement. Most patients required small to moderate amounts of PRN IV opioids, had acceptable pain control, and there were no significant adverse effects. Future large, prospective studies should evaluate dosing and timing for optimal patient outcomes.
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