Influence of Physostigmine on Patient-Controlled Analgesia (PCA) in Postoperative Intensive Care Patients (ANA06103)

Influence of Physostigmine on Patient-Controlled Analgesia (PCA) in Postoperative Intensive Care Patients, Considering Pain Score, Opioid Consumption, Hemodynamics and Cognitive Function

The study is to evaluate the influence of physostigmine in the postoperative period in intensive care patients considering pain quality, opioid consumption, hemodynamics and mobilisation.

Study Overview

• Status: Completed
• Conditions: Pain

Detailed Description

Pain management is of major concern in the postoperative period, mostly based on opioids. In numerous experimental and clinical trials cholinergic mechanisms have been demonstrated to play an important antinociceptive role. Physostigmine, a central cholineresterase inhibitor, has been shown to produce analgesia and enhance opiate analgesia after systemic injection. This action is not based on µ-receptor (opioid) activity, but can be mostly explained by stimulation of serotonine (5-HT-3) receptors. The major withdrawal of utilizating physostigmine in postoperative care, is due to its short duration of action.

In the present study, we examined the effect of a continuous intavenous physostigmine application during a patient-controlled analgesia with piritramide for 48 hours compared to a placebo infusion with NaCl.

Major concern was set for consumption of analgesics, VAS-pain scale, hemodynamics, mobilisation and side effects.

• Study Type: Observational
• Enrollment (Actual): 60

Contacts and Locations

Study Locations

• Germany
  • Ludwigshafen, Germany, D-67063
    • Klinkum Ludwigshafen, Department of Anesthesiology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Elective major surgery, postoperative ICU patients

Description

Inclusion Criteria:

• Age 18-80 years
• Indication for postoperative pain therapy and admission to ICU
• ASA I-III
• Weight 50-125 kg
• Patients that are willing to participate in the present study

Exclusion Criteria:

• Peridural anesthesia for pain management
• Severe left ventricular function (EF <30%)
• Severe/exacerbated COPD; Asthma
• ASA IV-V
• Chronic renal insufficiency(Creatinine > 1,5 mg/dl)
• Ulcera ventriculi
• Known allergy to any of the study agents
• Hb preoperative <9,5 g/dl
• Alcohol,drug and/or tablet abuse (Opioids, NSAR)
• Emergency operation
• Pregnancy
• Women of childbearing age and without a negative pregnancy test
• Severe liver disease (GOT oder GPT > 45 U/L)
• Severe neurologica derangements (e.g. M. Parkinson, Multiple Sklerosis)
• History of apoplexia <6 Monate or residua
• Perioperative myocardial infarction
• Patients that are not able to agree to the present study
• Patients that refuse to participate in the present study
• Patients that are part of any other study

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1-physostigmine; Physostigmine 4 mg in 50 ml NaCl 0.9% per 24 h as syringe pump continuously for 48 hours, plus physostigmine 2mg (in NaCl 0.9% 50 ml)at termination of sedation PCA: Patient-controlled analgesia with piritramide 1 mg/ml, on demand: bolus of 2 mg, maximum of 10 mg in 60 min
2-placebo; NaCl 0.9% 50 ml per 24 h continuously over 48 hours, plus 50 ml NaCl 0.9% at termination of sedation PCA: Patient-controlled analgesia with piritramid 1 mg/ml, on demand: bolus of 2 mg, maximum of 10 mg in 60 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
opioid consumption	48 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
pain quality (VAS) mobilisation hemodynamics side effects	operation to discharge from hospital

Collaborators and Investigators

• Sponsor: Klinikum Ludwigshafen
• Collaborators: University of Mannheim
• Investigators: Principal Investigator: Christoph Konrad, Prof., University Hospital Mannheim, Department of Anesthesiology; Study Director: Kerstin D. Roehm, MD, Klinikum Ludwigshafen, Department of Anesthesiology

Publications and helpful links

General Publications

• Passchier J, Rupreht J, Koenders ME, Olree M, Luitwieler RL, Bonke B. Patient-controlled analgesia (PCA) leads to more postoperative pain relief, but also to more fatigue and less vigour. Acta Anaesthesiol Scand. 1993 Oct;37(7):659-63. doi: 10.1111/j.1399-6576.1993.tb03784.x.
• Beilin B, Bessler H, Papismedov L, Weinstock M, Shavit Y. Continuous physostigmine combined with morphine-based patient-controlled analgesia in the postoperative period. Acta Anaesthesiol Scand. 2005 Jan;49(1):78-84. doi: 10.1111/j.1399-6576.2004.00548.x.
• Rohm KD, Riechmann J, Boldt J, Schollhorn T, Piper SN. Retracted: Do patients profit from physostigmine in recovery from desflurane anaesthesia? Acta Anaesthesiol Scand. 2007 Mar;51(3):278-83. doi: 10.1111/j.1399-6576.2006.01238.x. Epub 2007 Jan 23.
• Aiello-Malmberg P, Bartolini A, Bartolini R, Galli A. Effects of morphine, physostigmine and raphe nuclei stimulation on 5-hydroxytryptamine release from the cerebral cortex of the cat. Br J Pharmacol. 1979 Apr;65(4):547-55. doi: 10.1111/j.1476-5381.1979.tb07863.x.
• Rupreht J, Schneck HJ, Dworacek B. [Physostigmine--recent pharmacologic data and their significance for practical use]. Anaesthesiol Reanim. 1989;14(4):235-41. German.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: January 23, 2008
• First Submitted That Met QC Criteria: February 5, 2008
• First Posted (Estimate): February 6, 2008

Study Record Updates

• Last Update Posted (Estimate): February 6, 2008
• Last Update Submitted That Met QC Criteria: February 5, 2008
• Last Verified: December 1, 2007

More Information

Terms related to this study

• Keywords: pain; Hemodynamics; patient-controlled analgesia; postoperative analgesia; Side effects; Opioid consumption; Mobilisation; physostigmine; Pain quality (VAS Score)
• Other Study ID Numbers: ANA06103