January 2020

Synopsis: Baclofen is commonly prescribed as a muscle relaxant and for off-label use for alcoholism, GERD, nystagmus, and trigeminal neuralgia. It is renally excreted and 30 case reports tie new baclofen use to encephalopathy in patients with CKD. In this retrospective population-based cohort study of elderly (age 66+) patients with CKD (eGFR<60) in Ontario, cohorts were those newly prescribed >20mg/d of baclofen, those newly prescribed <20mg/d of baclofen, and those never prescribed baclofen. The primary outcome was hospitalization within 30d with encephalopathy (delirium, disorientation, transient alteration of awareness, TIA, unspecified dementia). The study analyzed 15,942 elderly patients with CKD who were new baclofen users between 2007-2018, 9,707 (60.9%) of whom were prescribed >20mg/d of baclofen initially. The primary outcome occurred in 1.11% of the high-dose group, 0.42% in the low-dose group, and 0.06% in the non-user group. Median time to hospitalization was 3d in the high-dose group and 8d in the low-dose group. Both groups of baclofen users had significant increased risk of hospitalization for encephalopathy compared to non-users (low dose: RR 5.90 [3.59-9.70], high dose: RR 19.8 [14.0-28.0]). In subgroup analysis, the risk of encephalopathy increased as eGFR decreased. Therefore, the study concludes that new baclofen use in an elderly population with CKD is associated with a significantly increased risk of hospitalization for encephalopathy in a potentially dose-dependent manner which may caution its use in this population. Limitations include observational study design with administrative data, uncertainty whether patients took medication as prescribed, and lack of serum baclofen levels at time of hospitalization. 

Synopsis: The optimal time of cholecystectomy for patients admitted with gallstone pancreatitis remains unclear. Historically, we have waited for resolution of symptoms of pancreatitis before electing to proceed with a cholecystectomy prior to discharge. However, recent studies have called into question the need for this delay in surgical management.

The authors of the study performed a randomized controlled trial in order to evaluate differences in outcomes between patients managed with early cholecystectomy within 24 hours compared to delayed cholecystectomy following resolution of symptoms of pancreatitis. In this single institution RCT, 97 patients with predicted mild gallstone pancreatitis were randomized to either laparoscopic cholecystectomy with cholangiogram within 24 hours versus delayed cholecystectomy. The authors hypothesized that cholecystectomy could be performed in an early fashion for mild gallstone pancreatitis without significant increase in complications while reducing overall length of hospital stay. 

Predicted mild pancreatitis was defined as a Bedside Index of Severity in Acute Pancreatitis (BISAP) score of 0 to 2 and no evidence of organ failure or local or systemic complications. 

The primary endpoint of the study was 30-day length of stay, secondary end-points included ERCP rates, complications, readmissions within 30 days, exacerbation of pancreatitis, and conversion to open cholecystectomy. Total 30-day LOS was significantly shorter in the early group (median LOS 50 h, IQR 27–82 h) when compared with the control group (median LOS 77 h, IQR 52–111 h), with IRR of 0.68, 95% CI 0.65–0.71, P < 0.005. Early cholecystectomy was associated with fewer ERCPs, 15% vs 30%, P = 0.038. Complication rates were low in both groups (6% vs 2%, P = 0.617). 

The major strength of this study is the prospective randomized design which eliminates bias based on surgeon perception of patient illness and therefore selection for surgery. This is still a fairly small trial and results warrant validation through larger study in a different patient population. A weakness of this study is the dependence on the reliability of the BISAP score for prediction of severity of pancreatitis. Importantly, a protocol amendment mandated a 12-hour delay prior to randomization in order to avoid error in prediction of severity of pancreatitis, after two patients progressed to more severe disease following initial study inclusion. 

Synopsis: This is a case-series of 500 patients with total parenteral nutrition-dependent catastrophic and chronic gut failure who were referred for surgical intervention (particularly transplantation) at the Cleveland Clinic-Center for Gut Rehabilitation and Transplantation between 8/1/2012-2/15/2019.

Their objective was to define the evolving role of integrative surgical management including transplantation for patients with gut failure. They offered an algorithm for management of patients with gut failure which is guided by: 1. clinical status, 2. Splanchnic organ (hepatic) function, 3. anatomy of residual gut, and cause of gut failure (See image below). Noteworthy, they advocate for gut transplant first if a patient presents with gut failure and concomitant liver failure or non-reconstructable gut. 

In their series, the mean age of patient was 45 ±17 years. Surgery was performed in 462 (92%) patients and 38 (8%) continued medical treatment. Definitive autologous gut reconstruction (AGR), which they defined as different reconstructive and remodeling procedures to reestablish gut continuity, restore normal alimentary flow, and modulate transit time, was achieved in 378 (82%) patients. Of the remainder, 42 (9%) had a primary transplant, and had 42 (9%) AGR followed by transplant. Among the transplant recipients, 27 (29%) had a liver along with the small bowel. There were a mean 1.9 autologous gut reconstructive surgeries per patient, and included primary reconstruction, interposition alimentary-conduits, intestinal/colonic lengthening, and reductive/decompressive surgery (check out the full text for lots of diagrams of surgeries and surgical options). 

Overall patient survival was 86% at 1-year and 68% at 5-years with restored nutritional autonomy in 63% and 78%, respectively. Autologous gut reconstruction had better long-term survival than transplantation (74% vs 50% at 5-years, p =0.03). TPN therapy alone had the worst 5-year survival at 44%. Transplant was superior at restoring nutritional autonomy (83% in transplant recipients vs. 71% in reconstructive patients alone). The team proposed a model for predicting restored nutritional autonomy which includes anatomy of restored gut (<200 cm, no gut and presence of ileocecal valve), duration and calories of TPN, cause of gut-failure, and serum bilirubin (link to clinical model in paper). 

Overall, surgical integration is an effective management strategy for gut-failure. The authors advocate for gut transplant only for patients who are not autologous gut reconstruction candidates (concurrent liver failure or non-reconstructable anatomy) or fail weaning of TPN therapy after multiple attempts at gut reconstruction. Of course, a main limitation of their data is confounding by indication but the Cleveland group’s experience show superior survival for patients who have reconstructive surgery alone.