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From the *Department of Anesthesiology, Faculty of Medicine, Shaheed Beheshti University; and Department of Immunology, Faculty of Medicine, Tehran University, Tehran, Iran.
Address correspondence and reprint requests to Ali Dabbagh, MD, Fellowship in Cardiac Anesthesia, Department of Anesthesiology, Taleghani Hospital, Velenjak, Chamran Exp Way, Tehran, Iran. Address e-mail to alidabbagh{at}yahoo.com.
Abstract
BACKGROUND: It has been demonstrated that chronic opium abusers have lower thresholds for pain. In this study we sought to determine whether chronic opium abuse has any effect on the duration of spinal block by local anesthetics.
METHODS: In a case-controlled study, 50 opium abusers and 50 nonabusers undergoing lower abdomen operations were selected from among the patients admitted to a university hospital for elective surgery. All patients received 100 mg hyperbaric preservative-free 5% lidocaine in dextrose, intrathecally.
RESULTS: The duration of anesthesia was much shorter in the opium abusers (60 ± 7 min) than in the nonabusers (83 ± 10 min) (P < 0.0001).
CONCLUSION: The study documents a shortened duration of spinal block in opium abusers.
The opioid analgesics, exemplified by morphine, are a common treatment of severe acute and chronic (both malignant and nonmalignant) pain states (1). Prolonged use of opioids is associated with progressive need for higher doses to achieve a constant analgesic effect, a phenomenon well known as analgesic tolerance. The exact mechanisms which underlie this phenomenon remain unclear (1–3), although a number of hypotheses have been proposed regarding the opioid receptors and the endogenous opioid peptides (4–7). New insights into pain and its regulation in opium abusers have been introduced (8–11). For instance, we have observed a shorter than expected duration of spinal anesthesia using intrathecal lidocaine for opium abusers. This clinical phenomenon could be linked to a number of previously observed conditions attributed to opioid tolerance (1,3,12–15).
This clinical study was planned to compare the duration of effect of intrathecal lidocaine in opium abuser and nonabuser patients undergoing similar surgical operations.
METHODS
This study met IRB requirements for human and animal trials and conformed to the criteria of the Ethics Committee, Department of Research Affairs, Faculty of Medicine, Shaheed Beheshti University of Medicine, Tehran, Iran. All patients gave written informed consent to participate in the trial.
In a descriptive-analytical, case–control, prospective study, the target population was all surgical patients being admitted to the hospital’s operating room, which was the study location, during a 6-mo period. One hundred patients (age 15–65 years and height 150–185 cm) scheduled for elective lower abdominal surgery were allocated into two groups according to their history of opium addiction. The opium group comprised chronic opium abusers, regularly using opium preparations orally or by inhalation, for at least 1 yr, all of whom described subjective symptoms of withdrawal from drug cessation. Patients in the control group, by self-report, had not used opium for the preceding 2 yr. Exclusion criteria were: patient refusal of subarachnoid block, abuse or illicit use of other controlled substances, preexisting cardiac or pulmonary disease, or any sign or clinical finding, denoting past or present neuropathy.
All patients were visited the night before surgery by the same anesthesiologist (one of the authors), and were informed about the study. A premedication dose of promethazine was also prescribed for 0.05 mg/kg IM administration 1 h before the surgery, accompanied by a 10 mg diazepam tablet per 70 kg body weight. In the case of chronic opium abuse, patients were told to use their usual daily dose; this was discussed in a private room with each opium abuser and the anesthesiologist who had visited the patient the evening before surgery. All patients were NPO for 8 h before the scheduled surgical procedure.
The anesthesiologist who performed the subarachnoid block and documented the sensory level was blinded to the patient’s history of opium abuse. After initiating standard monitoring (electrocardiogram, pulse oxymetry, noninvasive arterial blood pressure, and heart rate), the patients received 500–750 mL of lactated Ringer’s solution over 15–20 min. Subarachnoid blocks were performed with the patient in the sitting position under appropriate aseptic conditions. The L3–4 interspace was entered and a 24-gauge Whitacare spinal needle was inserted via a midline approach. The needle bevel was oriented cephalad while 100 mg of 5% preservative-free hyperbaric lidocaine with dextrose was injected at a rate of 2 mL every 5 s. The patients were placed supine after drug injection. All patients received 1 mg IV midazolam for sedation after spinal administration of the drug and a T6–T8 level of anesthesia was achieved with the help of position maneuvers. Sensory level was assessed with pinprick each minute thereafter for 10 min. The level of anesthesia was then checked and documented in 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, and 120 min after subarachnoid drug administration. If any patient had pain at any time during the operation, general anesthesia was induced immediately and the subarachnoid effects of the local anesthetic drug (spinal anesthesia) were considered to be terminated and, the final time of spinal anesthesia was recorded. The total time for effective spinal anesthesia was recorded from the drug injection time (as the start point) up to the time that a two-segment regression in the level of block (using a pinprick test) was detected.
Data entry and analysis were performed by S.P.S.S software (version 11.5). For data analysis, Student’s t-test and 
2 test were used as the statistical tests and a P value <0.05 was considered significant.
RESULTS
The two groups had no significant differences in respect to age, body weight, gender, or surgical duration (Table 1). In the opium abusers, the duration of opium abuse was 6.2 ± 1.8 yr. The most common pattern of abuse was inhalation (79.6% i.e., 39 patients among the abusers); the others (20.4%, i.e., 11 patients) abused opium orally. All the abusers used opium habitually and not as a prescribed drug. The average time interval between events of opium abuse in the abusers’ group was 30 ± 38 h.
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The duration of spinal anesthesia was significantly shorter in the abuser group (60 ± 7 min) than the nonabuser group (83 ± 10 min) (P < 0.0001).
Two patients among the nonabusers and three patients among the abusers had failed spinal anesthesia. They were excluded from the study and replaced by other qualified patients.
DISCUSSION
Factors affecting duration of block in spinal anesthesia include the type of local anesthetic, drug dosage and drug adjuvants such as opioids and epinephrine, among others (16). This study, however, demonstrated shortened duration of subarachnoid block in those patients who with a history of chronic opium abuse, a variable that has not previously been studied.
Although there was some difficulty in asking about a history of opium abuse, this was somewhat compensated for when the anesthesiologist was open and friendly the patients. Also, had it been possible to obtain objective documentation of opium abuse without ethical considerations, more precise data regarding the abuse may have resulted; however, this was not possible and only subjective assessments were considered. Likewise, it was difficult to assess the exact dose and time intervals of opium abuse. One of the other limitations of the study was that we did not assess motor block after intrathecal anesthesia, because of surgical limitations.
Administration of opioids typically results in analgesia. However, the opioid receptor system signals and modulates a multitude of effects and, under certain conditions, mediates hyperalgesia rather than analgesia (17). Many studies have tried to define the exact mechanisms creating opioid-induced hyperalgesia. Recent research suggests that opioid-induced hyperalgesia is complex, and involves multiple potential areas of pain amplification, including descending tonic facilitation originating in the rostral ventromedial medulla, the release of pronociceptive spinal dynorphin, and the potential interaction of excitatory amino acid neurotransmitters with other receptor systems. It is unclear whether these pain facilitating processes play a collective role in a phenomenon that mimics local anesthetic tolerance, whether there is some sort of cross-tolerance of local anesthetics with opioids, or whether other factors, e.g., voltage-gated sodium channel effects are involved. In addition to the classic opioid receptors a number of other receptors are affected by opioids both in the central and the peripheral nervous system (4–7,14,18) and, a number of studies have proposed some structural similarities between opioid and local anesthetic receptors in the spinal cord (9,10,19).
Future investigation is required to explain the clinical finding of shorter duration of intrathecal local anesthetic block in a variety of patients, especially those with altered pharmacokinetics (e.g., opium abusers). Further investigation may also help augment our understanding about transduction and the processing mechanisms of pain in the central nervous system (17).
The findings of this study suggest a shorter duration of neural block, after induction of spinal anesthesia with intrathecal administration of lidocaine, in chronic opium abusers compared with other, similar patients who are not abusing opium. This may be useful in selecting a local anesthetic drug and dose and the addition of adjuncts to prolong spinal blockade.
ACKNOWLEDGMENTS
The authors thank the administrative support of Department of Research Affairs, Faculty of Medicine, Shaheed Beheshti University of Medicine, Tehran, Iran in the course of the project. The authors also acknowledge the very kind help of Mrs. Soheila Moezzipur as the administrative coordinator of the study. And finally, the operating room authorities of Taleghani Hospital, Shaheed Beheshti University of Medicine, Tehran, Iran are highly appreciated, who handled the patients through their operation.
Footnotes
Accepted for publication April 10, 2007.
This study was performed as a research project in the Department of Anesthesiology, Taleghani Hospital, Faculty of Medicine, Shaheed Beheshti University, Tehran, Iran.
REFERENCES
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