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Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia: the START randomized clinical trial

 

Discussed by Dr Dan von Allmen

 

Bezerra JA, Spino C, Magee JC, Shneider BL, Rosenthal P, Wang KS, et al. Use of Corticosteroids After Hepatoportoenterostomy for Bile Drainage in Infants With Biliary Atresia: the START randomized clinical trial. JAMA. 2014 May 7;311(17):1750–10.

 

Abstract:

IMPORTANCE:

Biliary atresia is the most common cause of end-stage liver disease in children. Controversy exists as to whether use of steroids after hepatoportoenterostomy improves clinical outcome.

OBJECTIVE:

To determine whether the addition of high-dose corticosteroids after hepatoportoenterostomy is superior to surgery alone in improving biliary drainage and survival with the native liver.

DESIGN, SETTING, AND PATIENTS:

The multicenter, double-blind Steroids in Biliary Atresia Randomized Trial (START) was conducted in 140 infants (mean age, 2.3 months) between September 2005 and February 2011 in the United States; follow-up ended in January 2013.

INTERVENTIONS:

Participants were randomized to receive intravenous methylprednisolone (4 mg/kg/d for 2 weeks) and oral prednisolone (2 mg/kg/d for 2 weeks) followed by a tapering protocol for 9 weeks (n = 70) or placebo (n = 70) initiated within 72 hours of hepatoportoenterostomy.

MAIN OUTCOMES AND MEASURES:

The primary end point (powered to detect a 25% absolute treatment difference) was the percentage of participants with a serum total bilirubin level of less than 1.5 mg/dL with his/her native liver at 6 months posthepatoportoenterostomy. Secondary outcomes included survival with native liver at 24 months of age and serious adverse events.

RESULTS:

The proportion of participants with improved bile drainage was not statistically significantly improved by steroids at 6 months posthepatoportoenterostomy (58.6% [41/70] of steroids group vs 48.6% [34/70] of placebo group; adjusted relative risk, 1.14 [95% CI, 0.83 to 1.57]; P = .43). The adjusted absolute risk difference was 8.7% (95% CI, -10.4% to 27.7%). Transplant-free survival was 58.7% in the steroids group vs 59.4% in the placebo group (adjusted hazard ratio, 1.0 [95% CI, 0.6 to 1.8]; P = .99) at 24 months of age. The percentage of participants with serious adverse events was 81.4% [57/70] of the steroids group and 80.0% [56/70] of the placebo group (P > .99); however, participants receiving steroids had an earlier time of onset of their first serious adverse event by 30 days posthepatoportoenterostomy (37.2% [95% CI, 26.9% to 50.0%] of steroids group vs 19.0% [95% CI, 11.5% to 30.4%] of placebo group; P = .008).

CONCLUSIONS AND RELEVANCE:

Among infants with biliary atresia who have undergone hepatoportoenterostomy, high-dose steroid therapy following surgery did not result in statistically significant treatment differences in bile drainage at 6 months, although a small clinical benefit could not be excluded. Steroid treatment was associated with earlier onset of serious adverse events in children with biliary atresia.

 

Dr von Allmen’s comments:   

·                 Dr von Allmen would not use corticosteroids after Kasai procedure.

·                 The difference of bile drainage in the steroid group versus control (58.6% vs 48.6%) was not significant enough to continue use of corticosteroids.

 

 

Comparative Effectiveness of Skin Antiseptic Agents in Reducing Surgical Site Infections: A Report from the Washington State Surgical Care and Outcomes Assessment Program

 

Discussed by Dr George Whit Holcomb

 

Hakkarainen TW, Dellinger EP, Evans HL, Farjah F, Farrokhi E, Steele SR, et al. Comparative Effectiveness of Skin Antiseptic Agents in Reducing Surgical Site Infections: A Report from the Washington State Surgical Care and Outcomes Assessment Program. J Am Coll Surg. 2014 Mar 1;218(3):336–44.

 

Abstract:

BACKGROUND:

Surgical site infections (SSI) are an important source of morbidity and mortality. Chlorhexidine in isopropyl alcohol is effective in preventing central venous-catheter associated infections, but its effectiveness in reducing SSI in clean-contaminated procedures is uncertain. Surgical studies to date have had contradictory results. We aimed to further evaluate the relationship of commonly used antiseptic agents and SSI, and to determine if isopropyl alcohol has a unique effect.

STUDY DESIGN:

We performed a prospective cohort analysis to evaluate the relationship of commonly used skin antiseptic agents and SSI for patients undergoing mostly clean-contaminated surgery from January 2011 through June 2012. Multivariate regression modeling predicted expected rates of SSI. Risk adjusted event rates (RAERs) of SSI were compared across groups using proportionality testing.

RESULTS:

Among 7,669 patients, the rate of SSI was 4.6%. The RAERs were 0.85 (p = 0.28) for chlorhexidine (CHG), 1.10 (p = 0.06) for chlorhexidine in isopropyl alcohol (CHG+IPA), 0.98 (p = 0.96) for povidone-iodine (PVI), and 0.93 (p = 0.51) for iodine-povacrylex in isopropyl alcohol (IPC+IPA). The RAERs were 0.91 (p = 0.39) for the non-IPA group and 1.10 (p = 0.07) for the IPA group. Among elective colorectal patients, the RAERs were 0.90 (p = 0.48) for CHG, 1.04 (p = 0.67) for CHG+IPA, 1.04 (p = 0.85) for PVI, and 1.00 (p = 0.99) for IPC+IPA.

CONCLUSIONS:

For clean-contaminated surgical cases, this large-scale state cohort study did not demonstrate superiority of any commonly used skin antiseptic agent in reducing the risk of SSI, nor did it find any unique effect of isopropyl alcohol. These results do not support the use of more expensive skin preparation agents.

 

Dr Holcomb’s comments:

·           This paper would not change his choice of antiseptic agent. Dr Holcomb feels that iodine based agents and chlorhexidine agents are equally appropriate based on these results.

·           Dr Holcomb uses chlorhexidine and isopropyl alcohol for skin preparation.

 

 

Nonoperative Treatment With Antibiotics Versus Surgery for Acute Nonperforated Appendicitis in Children: a pilot randomized controlled trial

 

Discussed by Dr George Whit Holcomb

 

Svensson JF, Patkova B, Almström M, Naji H, Hall NJ, Eaton S, et al. Nonoperative Treatment With Antibiotics Versus Surgery for Acute Nonperforated Appendicitis in Children: a pilot randomized controlled trial. Annals of Surgery. 2015 Jan;261(1):67–71.

 

Abstract:

OBJECTIVE:

The aim of this study was to evaluate the feasibility and safety of nonoperative treatment of acute nonperforated appendicitis with antibiotics in children.

METHODS:

A pilot randomized controlled trial was performed comparing nonoperative treatment with antibiotics versus surgery for acute appendicitis in children. Patients with imaging-confirmed acute nonperforated appendicitis who would normally have had emergency appendectomy were randomized either to treatment with antibiotics or to surgery. Follow-up was for 1 year.

RESULTS:

Fifty patients were enrolled; 26 were randomized to surgery and 24 to nonoperative treatment with antibiotics. All children in the surgery group had histopathologically confirmed acuteappendicitis, and there were no significant complications in this group. Two of 24 patients in the nonoperative treatment group had appendectomy within the time of primary antibiotic treatment and 1 patient after 9 months for recurrent acute appendicitis. Another 6 patients have had an appendectomy due to recurrent abdominal pain (n = 5) or parental wish (n = 1) during the follow-up period; none of these 6 patients had evidence of appendicitis on histopathological examination.

CONCLUSIONS:

Twenty-two of 24 patients (92%) treated with antibiotics had initial resolution of symptoms. Of these 22, only 1 patient (5%) had recurrence of acute appendicitis during follow-up. Overall, 62% of patients have not had an appendectomy during the follow-up period. This pilot trial suggests that nonoperative treatment of acute appendicitis in children is feasible and safe and that further investigation of nonoperative treatment is warranted.

 

Dr Holcomb’s comments:

·                 This is a well done pilot study that shows that a larger randomized trial is needed.

·                 Long term follow-up is needed to determine the true risk of recurrent appendicitis after non-operative management.

 

 

Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study

 

Discussed by Dr Aaron Lipskar

 

Khan FA, Squires RH, Litman HJ, Balint J, Carter BA, Fisher JG, et al. Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study. J Pediatr. 2015 Jul;167(1):29–34.e1.

 

Abstract:

OBJECTIVES:

In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy.

STUDY DESIGN:

A multicenter, retrospective cohort analysis from the Pediatric Intestinal Failure Consortium was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with dependence on parenteral nutrition (PN) >60 days. Enteral autonomy was defined as PN discontinuation >3 months.

RESULTS:

A total of 272 infants were followed for a median (IQR) of 33.5 (16.2-51.5) months. Enteral autonomy was achieved in 118 (43%); 36 (13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified necrotizing enterocolitis (NEC; OR 2.42, 95% CI 1.33-4.47), care at an IF site without an associated intestinal transplantation program (OR 2.73, 95% CI 1.56-4.78), and an intact ileocecal valve (OR 2.80, 95% CI 1.63-4.83) as independent risk factors for enteral autonomy. A second model (n = 144) that included only patients with intraoperatively measured residual small bowel length found NEC (OR 3.44, 95% CI 1.36-8.71), care at a nonintestinal transplantation center (OR 6.56, 95% CI 2.53-16.98), and residual small bowel length (OR 1.04 cm, 95% CI 1.02-1.06 cm) to be independently associated with enteral autonomy.

CONCLUSIONS:

A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ileocecal valve, and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF.

 

Dr Lipskar’s comments:

·           It is counterintuitive that NEC is a protective factor for enteral autonomy.

·           It is difficult to make sense of the data as centers with transplant programs likely attract sicker patients.

·           This highlights the importance of intestinal failure patients being managed in a multidisciplinary intestinal failure program.

 Anesthetic neurotoxicity--clinical implications of animal models

 Discussed by Dr Aaron Lipskar

 Rappaport BA, Suresh S, Hertz S, Evers AS, Orser BA. Anesthetic neurotoxicity--clinical implications of animal models. N Engl J Med. 2015 Feb 26;372(9):796–7.

 

Abstract:

Some anesthetics and sedatives have been shown to cause neurotoxic effects in laboratory animals. The FDA collaboration SmartTots recommends undertaking large-scale clinical studies and avoiding nonurgent surgical procedures requiring anesthesia in children younger than 3 years of age.

 

Dr Lipskar’s comments:

·                 Until further trials in humans are conducted and provide more conclusive evidence, elective cases should be deferred until the age of 3.

·                 It may be difficult to define what constitutes an elective procedure in pediatric surgery.

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