The subjects were selected via simple convenience sampling. In this regard, all candidates for lower-limb orthopedic surgery were enrolled in the study after meeting the inclusion criteria. Following that, the participants were divided into two 60-member groups of drug-dependent and non-dependent patients, in accordance with their history of drug abuse. Similarly, the sample size was estimated at 120 with reference to the relevant literature and based on the sample size calculation formula 5.

The inclusion criteria included the age range of 20-50 years, possibility of using spinal anesthesia for the person, lack of coagulation disorders, no history of cardiovascular diseases, no diabetes, no diseases leading to neuropathy, no simultaneous addiction to non-opioids, lack of backbone disorders, no head trauma with high intracranial pressure, fracture of a lower limb, and patient’s willingness to participate in the study. The exclusion criteria were lack of willingness to cooperate with the researcher, failure of spinal anesthesia and the need to have general anesthesia, feeling pain during the surgery, and the need to inject narcotics during the surgery.

One day before the surgery, an anesthesiologist (the researcher) visited all patients and cardiovascular counseling, along with echocardiography, was conducted for all of patients after the visit. To alleviate pain in the drug-dependent patients prior to surgery, they were allowed to use their typical narcotics with their routine methods. In addition, 5 mg of morphine was injected intramuscularly in the gluteal muscle if the pain was persistent. It should be noted that just 5 mg of intramuscular morphine was injected into the non-dependent group, and only in the presence of pain. Since patients must fast for 8 hours before to surgery (NPO: nil per os/nothing by mouth), the infusion of 10 cc/kg of dextrose saline serum was started from the beginning of NPO and continued until the onset of the surgery. At the beginning of the surgery, the infusion of 10 cc/kg of serum ringer was initiated through the peripheral veins, followed by pulse oximetry screening and cardiac monitoring. After that, 4 cc of 0.5% bupivacaine (20 mg) was injected by needle (No. 25) between vertebrae L3-L4 in the subarachnoid space under sterilized conditions in a sitting position by an anesthesiologist, who was unaware of the patients’ placement in the study groups.

In the next stage, the participants were put in the dorsal recumbent position and were intravenously administered with 2 mg of midazolam for sedation. In addition, mask oxygen therapy was performed at 6 L/min. After 5 minutes, the pinprick test was performed to confirm the effectiveness of spinal anesthesia. The given test was repeated every 10 minutes during the surgery. If the anesthesia was ineffective at any stage of the test, general anesthesia was applied and the patients were excluded from the study. However, if the anesthesia was effective, the patients’ surgery was conducted by an orthopedist, who was unaware of the patients’ placement in the study groups. Following that, the duration of the patients’ anesthesia after the surgery, along with the demographic characteristics and history of drug abuse, were recorded for each patient in pre-designed forms.

Data analysis was performed using the statistics program SPSS (version 24), with descriptive statistics, Chi-square test, and independent t-test.

In this research study, 72 (60%) patients were male and 48 (40%) participants were female. According to the results, no significant difference was observed between the study groups in terms of gender, considering the results of the Chi-square (P=0.60). The mean age of the patients was 37.4±5.7 years, wherein there were 16 (13.3%), 69 (57.5%), and 35 (29.2%) individuals in the age groups of 20-30, 30-40, and 40-50 years, respectively. Moreover, no significant difference was observed in the mean age of the study groups (P=0.863). On the other hand, the mean duration of drug abuse in the drug-dependent group was reported to be 7.5±1.3 years. Furthermore, 44 (73.3%) and 16 (26.7%) of the participants had a history of drug abuse in inhalant and oral forms, respectively. Comparison of the spinal anesthesia duration between the two groups indicated a shorter period in the drug-dependent patient group, as compared to the other patient group (non-dependent). In addition, the effect of spinal anesthesia in these patients was eliminated earlier, and this difference was statistically significant (Table 1).

Table 1

Group/Variable	Drug-dependent	Non-dependent	P-value
Duration of spinal anesthesia with bupivacaine	91.7±14.8(standard deviation±mean)	132.5±18.1(standard deviation±mean)	0.0001

From comparison of results based on the type of drug intake (oral versus inhalant), it was demonstrated that in inhalant abusers, spinal anesthesia was higher, as compared to oral drug users. While there was a slight difference in the mean duration, it was statistically significant (Table 2).

Table 2

Group/Variable	Inhalantn=44	Oral n=16	P-value
Duration of spinal anesthesia with bupivacaine	92.8±12.6 (standard deviation±mean)	88.7±9.9 (standard deviation±mean)	0.0001

The results of this study showed that the duration of spinal anesthesia was significantly shorter in the drug-dependent patients, compared to the non-dependent individuals. It should be noted that the effect of narcotic compounds on the body’s pain system can be induced not only by conventional opioid receptors but by other numerous receptors in the central and peripheral nervous systems, which can be significantly affected by such compositions 10. Among chronic drug abusers, the responses of opioid receptors to painful stimuli fluctuate. In this respect, frequent substance abuse can lead to a connection between opioids and receptors, thereby preventing the proper transcription of DNA and production of non-natural proteins, which can result in hyperalgesia and allodynia 111121314.

Moreover, the immune response of such patients is altered and there is an increase in the ratio of pro-inflammatory interleukins to anti-inflammatory interleukins.

These above factors suggest a decrease in the relative effect of anesthesia medications during surgery as well as the potential need for a higher dose of medicine to control the patients’ pain and stress. As these have not been proven, further studies would be helpful in this regard 15161718. In a study by Sadeghi et al., the duration of spinal anesthesia in drug-dependent and non-dependent patients was measured. Sadeghi et al. divided the subjects into four groups. In the first group, consisting of non-dependent individuals, hyperbaric bupivacaine with 1 cc of saline was injected; in the second group encompassing non-dependent patients, bupivacaine with sufentanil was injected; in the third group containing drug-dependent subjects, placebo and intrathecal bupivacaine were injected; and finally in the fourth group (the drug-dependent patients), sufentanil and intrathecal bupivacaine were injected. After that, the start time and duration of anesthesia in the study groups were measured and compared. According to the results, there was a shorter duration of spinal anesthesia in the third group, compared to the other study groups. It was concluded that adding 5 mg of intrathecal sufentanil to the patients’ local anesthesia could make the duration of their spinal anesthesia equivalent to that of non-dependent patients 3.

Despite the difference in the type of drug used in the aforementioned and present studies, our findings are in agreement with the results obtained by Sadeghi and colleagues 3. In line with the results of the present study, Dabbagh et al. (2007) reported that the duration of spinal anesthesia in opioid abusers and control groups were 86.6±15.7 and 162±22.1 minutes, respectively, and that this difference was statistically significant. This study also indicated that the duration of spinal anesthesia with bupivacaine was shorter in the groups of opioid abusers, which was probably due to the cross-resistance between the anesthesia area and the opioid compounds in the spinal neurons 5. In a research by Karbasy et al. (20), however, when the levels and duration of spinal anesthesia with bupivacaine in drug-dependent and non-dependent individuals were compared, a significantly longer duration of spinal anesthesia in drug-dependent patients and lower levels of spinal anesthesia were observed, as compared to non-dependent individuals.

One of the major drawbacks of the study herein was the lack of evaluation of the levels and duration of spinal anesthesia. Nevertheless, the obtained results confirmed that using bupivacaine might be insufficient for inducing anesthesia in drug-dependent individuals 19. Furthermore, in a study by Hashemian et al. on drug-dependent and non-dependent patients with hand injury, it was reported that the drug-dependent patients required higher doses of lidocaine for injury block. In addition, the results were indicative of a significantly longer starting time for these individuals 20. Certainly, one should pay particular attention to the fact that in Iranian culture, it is a social disgrace to admit your addiction. Another major limitation of this study is the reliance of accurate data on self-reporting (especially about addiction). This impacts placement of patients in the correct group (drug-dependent versus non-dependent). For example, a patient may have an addiction to a drug but not find that addiction bothersome; thus, they may be placed wrongly in the non-dependent group as opposed to dependent group. It is also worth noting that patients’ dissatisfaction with performing the addiction test for entering into the study was an unresolved issue, which might have contributed to the distortion of the final results.

According to the results of the study, there was a significantly shorter duration of spinal anesthesia in the drug-dependent individuals, compared to the non-dependent subjects. Therefore, spinal anesthesia can only be used in short-term surgeries for drug dependent people. In general, it is recommended that general anesthesia be used for these patients in surgeries that may last more than an hour.

The authors declare that there is no conflict of interest regarding the publication of this article.

The study was financially supported by Zahedan University of Medical Sciences, Zahedan, Iran.

Faranak Beirami: advising in development of research and revising this paper.

Masoum Khoshfetrat: participating in the implementation of research and supervising the data collection and revising the paper.

Hadi Khosravi: participating in the implementation of research and data collection.

Aliakbar Keykha: Compiling and editing the paper. All authors reviewed, commented and approved the final version.

This article was extracted from a thesis written by a resident of anesthesiology and critical care, approved and funded by Research and Technology Deputy of Zahedan University of Medical Sciences. Hereby, we extend our gratitude to the Research and Technology Deputy of the University. In addition, we would like to thank the staff and orthopedic surgery ward at the Khatam-ol-Anbia Hospital of Zahedan for assisting us in this research.