1. Patients
The present prospective, randomized, double blind, placebo control study was conducted in the Department of Anaesthesiology and Critical Care of Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak after obtaining approval from the institutional ethics committee of Pandit Bhagwat Dayal Sharma Post Graduate Institute of Medical Sciences, Rohtak (Endst No. Surg. I/16/537-74 dtd 17/2/2016). Seventy-five adult patients (age group, 18–65 years) of either sex, with an American Society of Anesthesiologists (ASA) physical status 1 and 2 and undergoing elective thoracolumbar spinal instrumentation for isolated spinal trauma requiring laminectomy (minimum one level and maximum three levels) were enrolled in the study after they provided informed written consent. Patients who were already on the study drug; had a history of allergy to the study drug; had epilepsy, liver, or kidney diseases; were pregnant or lactating; had a psychiatric illness, drug or alcohol abuse; were on beta blockers; and those who receiving narcotics within 24 hours of the surgery were excluded. Patients with other injuries (chest, abdominal, head, long bones, etc.) were also excluded.
During pre-anesthetic rounds, the detailed clinical history was taken, clinical examination was performed, and anthropometric parameters were evaluated. Routine investigations and special investigations were conducted as per requirement. The purpose and protocol of the study and scoring of pain as per the Visual Analog Scale (VAS) was explained to the patients. Adequate fasting of 6 hours before the surgery was advised, and premedication was given in the form of a 150-mg tablet of ranitidine orally the night before and in the morning 2 hours before the surgery.
Patients were randomly allocated to either of the following three groups using a computer-generated sequence of random numbers: group P (n=25) received pregabalin capsule (150 mg, PREGABID-150; Intas Pharmaceuticals Ltd., Dehradun, India), group C (n=25) received clonidine tablet (150 mcg, ARKAMIN-100; Unichem, Mumbai, India), and group N (n=25) received placebo (calcium tablet) 90 minutes before the surgery with a sip of water.
On arrival in the operating room, an intravenous line was secured. Routine monitoring, including heart rate (beats per minute), electrocardiogram, non-invasive blood pressure, and pulse oximetry (SpO2) was performed using Philips Intellivue MP50 monitor. General anesthesia was induced using fentanyl 2 mcg kg-1, sleep dose of thiopentone (incremental dose was administered till loss of eyelash reflex) was given, and orotracheal intubation was facilitated with vecuronium 0.10 mg kg-1. Intraoperatively, end tidal carbon dioxide, temperature, bispectral index (BIS), and inspired/expired concentration of isoflurane were also monitored.
Before the surgery, the incision site was infiltrated by the surgeon using lignocaine 1% with adrenaline 1:2,00,000. In all the patients, surgery was performed via the open and posterior approach in the prone position. Laminectomy of required levels was performed to perform cord decompression followed by fixation of the spine using pedicle and screw. Anesthesia was maintained with oxygen (35%) and nitrous oxide (65%) in isoflurane (minimum alveolar concentration titrated to keep BIS 40 to 60) and intermittent vecuronium (0.02 mg kg-1), whenever indicated. Fluid management and blood transfusion was done as per standard protocol.
Following surgery completion, isoflurane was discontinued after skin suturing, and nitrous oxide was stopped after the patient was made to lie in the supine position. Neuromuscular blockade was reversed with neostigmine 50 mcg kg-1 and glycopyrrolate 10 mcg kg-1, and extubation was done when adequate spontaneous ventilation was established. Emergence time (time from switching off nitrous oxide until the opening of eyes), and extubation time (time from switching off nitrous oxide until tracheal extubation) was noted. Patients sedation level (as per Ramsay Sedation Scale), pain at rest and during movement (while coughing) was assessed using the VAS score. Postoperative nausea and vomiting, shivering, or any other complaints, such as dry mouth, visual disturbances, and headache were noted and managed appropriately.
In the recovery room, the patients’ recovery was graded as per the Modified Aldrete Score (MAS). A maximum score of 9 was considered because many of our patients had paraplegia, and movement of the lower limbs could not be demonstrated.
Time of giving the first rescue analgesic, defined as the period from surgery to when the first dose of analgesia was administered at patient’s request (VAS >3), was recorded. On pain, fentanyl 1 mcg kg-1 was administered intravenously followed by 0.5 mcg kg-1 in case of VAS >3 with a maximum dose of 2 mcg kg-1 in 1 hour. Ketorolac injection (30 mg) was given as rescue analgesic and repeated every 8 hours, whenever required. The patients’ vital parameters, sedation level, and pain score, both at rest (VAS static) and during movement (VAS dynamic) were recorded at 0, 1, 2, 4, 6, 12, and 24 hours. The total dose of analgesics, fentanyl and ketorolac, antiemetic administered in 24 hours was also recorded.
2. Statistical analyses
A sample size of 75 patients (25 patients in each group) was used to detect a significant difference of 20% in the fentanyl consumption with a power of 85% and a significance level of 5%.
The data obtained were compiled and analyzed using IBM SPSS ver. 20.0 (IBM Corp., Armonk, NY, USA). Quantitative data were analyzed using one-way analysis of variance (one-way analysis of variance). Qualitative data were analyzed using chi-square test for the ASA grading, sex, VAS score, and time for first rescue analgesic and Fisher exact test for adverse events. Post-hoc analyses using Bonferroni test was used for multiple comparisons.
Normally distributed data are presented as mean±standard deviation values, and categorical data are presented as frequencies and percentages. A p-value <0.05 was considered significant.