Beneficial effects of theophylline infusions in surgical patients with intra-abdominal hypertension

Langenbecks Arch Surg. 2011 Aug;396(6):793-800. doi: 10.1007/s00423-011-0808-5. Epub 2011 Jun 3.

Abstract

Background: Intra-abdominal hypertension (IAH) can cause high mortality. Recently, we found that IAH was associated with increased serum levels of adenosine and interleukin 10. Our present "hypothesis-generated study" was based on the above mentioned results.

Materials and methods: In this uncontrolled clinical trial, a total of 78 patients with IAH were enrolled representing a 13-20 mmHg range of intra-abdominal pressure (IAP). Patients requiring surgical abdominal decompression were excluded. Patients were treated with the following protocols: standard supportive therapy (ST, n = 38) or ST plus infusion with the adenosine receptor antagonist theophylline (T, n = 40). Over the 5-day measurement period, IAP was monitored continuously and serum adenosine concentration and other clinical and laboratory measurements were monitored daily. Mortality was followed for the first 30 days following the diagnosis of IAH.

Results: Mortality of ST patients was 55%, which is compatible to other studies. Serum adenosine concentration was found to be directly proportional to IAP. Of the 40 patients receiving T treatment, survival was 100%. An increased survival related to theophylline infusion correlated with improving serum concentrations of IL-10, urea, and creatinine, as well as 24-h urine output, fluid balance, mean arterial pressure, and O(2)Sat.

Conclusions: Adenosine receptor antagonism with T following IAH diagnosis resulted in markedly reduced mortality in patients with moderated IAH (<20 mmHg). Theophylline-associated mortality reduction may be related to improved renal perfusion and improved MAP, presumably caused by adenosine receptor blockade. Because this study was not a randomized controlled study, these compelling observations require further multicentric clinical confirmation.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • APACHE
  • Abdomen*
  • Adenosine / blood
  • Biomarkers / blood
  • Compartment Syndromes / drug therapy*
  • Compartment Syndromes / mortality
  • Compartment Syndromes / physiopathology
  • Cytokines / blood
  • Decompression, Surgical
  • Female
  • Humans
  • Infusions, Intravenous
  • Male
  • Middle Aged
  • Postoperative Complications / drug therapy*
  • Postoperative Complications / mortality
  • Postoperative Complications / physiopathology
  • Purinergic P1 Receptor Antagonists / therapeutic use*
  • Theophylline / administration & dosage
  • Theophylline / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Cytokines
  • Purinergic P1 Receptor Antagonists
  • Theophylline
  • Adenosine