THE EFFECT OF CHRONIC SSRI/SNRI ANTIDEPRESSANT TREATMENT ON PROPOFOL CONSUMPTION IN ELECTIVE SPINE SURGERY

Overview

THE GOAL OF THIS OBSERVATIONAL STUDY IS TO LEARN WHETHER LONG-TERM USE OF SELECTIVE SEROTONIN REUPTAKE INHIBITOR (SSRI) OR SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITOR (SNRI) ANTIDEPRESSANTS IS RELATED TO THE AMOUNT OF PROPOFOL NEEDED DURING PLANNED SPINE SURGERY. PROPOFOL IS A MEDICINE GIVEN THROUGH A VEIN TO PRODUCE AND MAINTAIN ANESTHESIA. THE MAIN QUESTIONS THIS STUDY AIMS TO ANSWER ARE: * DO PATIENTS WHO REGULARLY TAKE AN SSRI OR SNRI NEED A DIFFERENT TOTAL AMOUNT OF PROPOFOL DURING SURGERY THAN PATIENTS WHO DO NOT TAKE THESE MEDICINES? * ARE THERE DIFFERENCES IN PROPOFOL AND REMIFENTANIL USE, DEPTH OF ANESTHESIA, VITAL SIGNS, OR RECOVERY TIME BETWEEN THE STUDY GROUPS? THE STUDY WILL INCLUDE 216 ADULTS UNDERGOING PLANNED SPINE SURGERY. RESEARCHERS WILL COMPARE 108 PARTICIPANTS WHO REGULARLY TAKE AN SSRI OR SNRI WITH 108 PARTICIPANTS WHO DO NOT TAKE THESE MEDICINES. ALL PARTICIPANTS WILL RECEIVE ROUTINE ANESTHESIA CARE. THE STUDY WILL NOT START, STOP, OR CHANGE ANY ANTIDEPRESSANT TREATMENT, AND PARTICIPANTS WILL NOT BE RANDOMLY ASSIGNED TO A GROUP. RESEARCHERS WILL RECORD THE AMOUNT OF PROPOFOL AND REMIFENTANIL USED DURING SURGERY, BLOOD PRESSURE, HEART RATE, OXYGEN LEVEL, DEPTH OF ANESTHESIA, AND RECOVERY TIME.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS) AND SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS (SNRIS) ARE CONSIDERED FIRST-LINE PHARMACOLOGICAL AGENTS IN THE TREATMENT OF DEPRESSION AND ANXIETY DISORDERS (1). THESE DRUGS SELECTIVELY INCREASE SEROTONIN CONCENTRATIONS IN THE SYNAPTIC CLEFT BY INHIBITING THE SEROTONIN TRANSPORTER (SERT); THEY SUPPRESS NOREPINEPHRINE AND DOPAMINE REUPTAKE ONLY MINIMALLY (1). HOWEVER, SSRI AND SNRI AGENTS HAVE THE POTENTIAL TO CAUSE HYPERTENSIVE EFFECTS (2). THE HYPERTENSIVE MECHANISM IS ASSOCIATED WITH SSRIS RAISING SYNAPTIC SEROTONIN LEVELS THROUGH SERT INHIBITION, RESULTING IN OVERSTIMULATION OF 5-HT1A AND 5-HT2A RECEPTORS (3). SEROTONIN EXCESS ACTIVATES THE SYMPATHETIC NERVOUS SYSTEM, TRIGGERING VASOCONSTRICTION, TACHYCARDIA, AND CATECHOLAMINE RELEASE, LEADING TO AN INCREASE IN BLOOD PRESSURE; THIS INDIRECTLY INCREASES THE NEED FOR INTRAOPERATIVE ANESTHETIC (4). ADDITIONALLY, SSRIS-ESPECIALLY POTENT CYP2D6 INHIBITORS SUCH AS PAROXETINE AND FLUOXETINE-CAN REDUCE THE ANALGESIC EFFECTS OF PRODRUG-TYPE OPIOIDS (E.G., CODEINE, HYDROCODONE, AND TRAMADOL) BY INHIBITING THEIR METABOLISM (5). THIS INTERACTION BLOCKS THE CONVERSION OF PRODRUGS TO ACTIVE METABOLITES (CODEINE → MORPHINE; HYDROCODONE → HYDROMORPHONE) VIA THE CYP2D6 ENZYME IN THE LIVER, REDUCING PLASMA ACTIVE OPIOID CONCENTRATIONS AND DISRUPTING Μ-OPIOID RECEPTOR ACTIVATION; ULTIMATELY LEADING TO A HIGHER OPIOID DOSE REQUIREMENT FOR PATIENTS (5). AS A PARALLEL MECHANISM, SEROTONIN EXCESS (AT HIGH DOSES OR IN INTERACTION WITH OTHER AGENTS) CAN INDUCE SEROTONIN-INDUCED HYPERALGESIA; THIS PROCESS OCCURS THROUGH STIMULATION OF THE CAMP SECONDARY MESSENGER SYSTEM VIA 5-HT1A RECEPTORS IN PERIPHERAL NERVE ENDINGS AND POTENTIATES THE TENDENCY TOWARDS HYPERALGESIA (6). CONSIDERING THESE DESCRIBED MECHANISMS, MAINTAINING A CONSTANT REMIFENTANIL DOSE DURING THE INTRAOPERATIVE PERIOD MAY INCREASE PROPOFOL CONSUMPTION (7). HOWEVER, DESPITE THIS THEORETICAL INFORMATION, THE EFFECT OF SSRI-SNRI USE ON PROPOFOL CONSUMPTION DURING THE PERIOPERATIVE PERIOD HAS NOT BEEN SUFFICIENTLY INVESTIGATED. THEREFORE, THIS STUDY WILL INVESTIGATE THE RELATIONSHIP BETWEEN THESE TWO FACTORS.