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The Intraoperative Effect of Methadone on Somatosensory Evoked Potentials

Higgs, Maureen MD; Hackworth, Robert J. MD; John, King AuD, CCC-A, CNIM; Riffenburgh, Robert PhD; Tomlin, Jeffrey MD; Wamsley, Brian MD

Journal of Neurosurgical Anesthesiology: April 2017 - Volume 29 - Issue 2 - p 168–174
doi: 10.1097/ANA.0000000000000265
Clinical Report

Background: Evoked potentials (EP), both somatosensory evoked potentials (SSEP) and transcranial motor evoked potentials (TcMEP), are often used during complex spine surgery to monitor the integrity of spinal pathways during operations in or around the spine. Changes in these monitored EP signals (increased latency and decreased amplitude) may result from ischemia, direct surgical injury, changes in blood pressure, hypoxia, changes in CO2 tension, and anesthetic agents. Typically, a clinically significant change for SSEPs is defined as an increase in latency >10% or a decrease of amplitude >50%. A clinically significant change for TcMEPs is much more complex but is also described in terms of large signal loss or decrease. Opioids have been shown to both increase latency and decrease the amplitude of SSEPs, although this change is usually not clinically significant. There has been a renewed interest in methadone for use in spine and other complex surgeries. However, the effect of methadone on intraoperative monitoring of SSEPs and TcMEPs is unknown. We present the first study to directly look at the effects of methadone on SSEP and TcMEP monitoring during complex spine surgery.

Methods: The goal of this study was to observe the effect of methadone on an unrandomized set of patients. The primary endpoint was methadone’s effect on SSEPs, and the secondary endpoint was methadone’s effect on TcMEPs. Adult patients undergoing spine surgery requiring intraoperative neuromonitoring were induced with general anesthesia and had a baseline set of SSEPs and TcMEPs recorded. Next, methadone dosed 0.2 mg/kg/lean body weight was given. Repeat SSEPs and TcMEPs were recorded at 5, 10, and 15 minutes, with the timing based on distribution half-life of methadone between 6 and 8 minutes. Postoperatively, adverse events from methadone administration were collected.

Results: There was a statistically significant difference found in SSEPs for N20 latency (95% confidence interval [CI], 0.17-0.53; P=0.028), P37 latency (95% CI, 0.65-1.25; P=0.001), and N20 amplitude (95% CI, 0.09-0.32; P=<0.001), but not for P37 amplitude (95% CI, −0.19 to 0.00; P=0.634). There was no significant effect found for TcMEPs, the secondary endpoint of the study, and there were minimal adverse events recorded postoperatively.

Conclusions: The data demonstrate that a single intravenous dose of methadone has a statistically significant difference on the amplitude and latency of SSEPs. However, this statistical difference does not translate into a clinical significance.

Department of Anesthesia, Naval Medical Center San Diego, San Diego, CA

M.H. and R.J.H.: helped design the study, conduct the study, analyze the data, and write the manuscript. J.K. and B.W.: helped conduct the study, analyze the data, and write the manuscript. R.R.: helped design the study, analyze the data, and write the manuscript. J.T.: helped critical review and evaluation of the manuscript.

The authors have no funding or conflicts of interest to disclose.

Address correspondence to: Robert J. Hackworth, MD, Department of Anesthesia, Naval Medical Center San Diego, 34800 Bob Wilson Dr., San Diego, CA 92134 (e-mail:

Received June 16, 2015

Accepted November 12, 2015

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