Comparison Between Intravenous and Intrathecal Clonidine in Post-cesarean Analgesia

METHODS Patients The research was submitted and approved by the Clinics Hospital of University of São Paulo Ethics in Research Board (CAAE 05847312.8.0000.0068, Nº 940.941). Patients authorized their participation and the proposed interventions and data collection, through signature of Free Consent Term.

Inclusion criteria were women aged 18 years or older, in term pregnancy, who underwent elective cesarean (no labor). Exclusion criteria was the following: multiple pregnancy; moderate or several systemic disease, categorized as American Society of Anesthesiology physical status (ASA) higher or equal to 3; contraindications for spinal anesthesia; contraindications for the drugs involved in the study; uncontrolled high blood pressure or diabetes mellitus in need of insulin therapy; intravenous psychotropic drugs users; previously known malformation on the fetus; and patients with previous history of chronic pain.

Patients anesthetic management All volunteers were managed according to the hospital protocol for cesarean delivery, and the one difference between groups was the clonidine or placebo given intrathecally or intravenously. Multiparameter non-invasive monitoring was used. The patients received a intravenous 10ml/kg Ringer Lactate bolus during realization of spinal anesthesia with heavy Bupivacaine 0,5% (15mg), morphine 0,02 (80mcg) and fentanyl (10mcg). Blood pressure was measured non-invasively during intra-operative period, each 1 minute until the baby was born, and each 3 minutes after the delivery. Low blood pressure was treated with Metaraminol 0,2mg intravenous bolus and/or Ephedrine 5mg intravenous bolus. Bradycardia was defined as heart rate inferior to 45 beats per minute, and treated with Atropine 0,5mg intravenous bolus. Intra-operative rescue analgesia was provided, if necessary, according to the patients needs or if the assistant anesthetist felt that it was necessary, with Fentanyl intravenous bolus, until a maximum dose of 100mcg. Before the skin incision, the patient received cefazolin 2g IV. After cord clamp, patients received Oxytocin 5 international units diluted in Ringer Lactate 250ml, ketoprofen 100mg IV, Dipyrone 2g IV, Omeprazole 40mg IV, Ondansetron 8mg IV. After procedure, the women were driven to Post Anesthetic Care Unit (PACU). There, if they felt pain, they could receive morphine 2mg IV, each 5 minutes, according to the patients needs. Post-operative pain control in the ward was standardized on the following protocol: ketoprofen 100mg IV 12/12h, Dipyrone 2g IV 6/6h; Tramadol IV 100mg maximum 8/8h, if uncontrolled pain. If pain persists, morphine subcutaneously, 5mg could be administered by nurse, 4/4h. Nauseas were treated with Dimenhydrinate 50mg IV 6/6h and Metoclopramide 10mg IV 8/8h, and itch was attenuated with Diphenhydramine 25mg IV, in case of such symptoms.

A neonatology team was present in every delivery and was responsible for the first evaluation of the newborn, including Apgar score and resuscitation.

Groups and interventions The included patients were randomly divided into one of three groups. The professional who administered the drugs was external to de research group, and did it unblinded. The researcher who did the assessments of the variables was blind for what intervention had been made. In control group, patients received placebo intravenously and intrathecally. In the intrathecal clonidine group, patients received 75 mcg of spinal clonidine, and intravenous placebo. In the intravenous clonidine group, patients received 75 mcg of intravenous clonidine, and spinal placebo. The solutions volumes were the same in all three groups, by 0,9% saline fluid addition to intrathecal and intravenous infusions.