Clinical trial NCT00608621: Influence of Physostigmine on Patient-Controlled Analgesia (PCA) in Postoperative Intensive Care Patients
Official title: Influence of Physostigmine on Patient-Controlled Analgesia (PCA) in Postoperative Intensive Care Patients, Considering Pain Score, Opioid Consumption, Hemodynamics and Cognitive Function
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Pain
Keywords: physostigmine
postoperative analgesia
pain
patient-controlled analgesia
Opioid consumption
Pain quality (VAS Score)
Hemodynamics
Mobilisation
Side effects
Lead sponsor: Klinikum Ludwigshafen
Sponsor class: OTHER
Collaborators: name: University of Mannheim
First posted: 2008-02-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Elective major surgery, postoperative ICU patients

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: opioid consumption
timeFrame: 48 hours
Secondary outcomes:
measure: pain quality (VAS) mobilisation hemodynamics side effects
timeFrame: operation to discharge from hospital
Other outcomes:
Locations:
city: Ludwigshafen
country: Germany
facility: Klinkum Ludwigshafen, Department of Anesthesiology
Study officials:
affiliation: University Hospital Mannheim, Department of Anesthesiology
name: Christoph Konrad, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: Klinikum Ludwigshafen, Department of Anesthesiology
name: Kerstin D. Roehm, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Rupreht J, Schneck HJ, Dworacek B. [Physostigmine--recent pharmacologic data and their significance for practical use]. Anaesthesiol Reanim. 1989;14(4):235-41. German.