Opioid Group Research Articles

Epidemiology of adverse effects of prehospital sedation analgesia

The aim of this study was to introduce a continuous monitoring of side effects related to sedation-analgesia in the field. A document was completed by physicians on board the ambulances for all prehospital interventions and checked daily by the medical staff. A total of 3605 interventions were evaluated over a 12-month period. Six hundred four patients undertook analgesia and/or sedation: group 1 (spontaneously breathing patients) n = 289 and group 2 (intubated-ventilated patients) n = 315. Sixty-four percent of patients received intravenous opioids in group 1. The anesthetic technique used for intubation was the rapid sequence induction in 70% of patients. Side effects were observed in 5.5% in group 1 (nausea: 2%, hypotension: 1%, hypoxemia: 1%) and 22% of patients in group 2 (hypotension-arrhythmia: 12%, cardiac arrest: 2%, difficult intubation: 5%, hypoxemia: 1%, pulmonary aspiration: 1%, laryngospasm/bronchospasm: 2%). No death was related to these medications. A close monitoring of side effects related to sedation-analgesia must be included in a quality program to improve patient safety in the field.

The impact of neuraxial analgesia on the progress and outcome of labor

Epidural analgesia is an extremely popular form of labor pain relief. This popularity has led to careful examination of the effects of epidural analgesia on labor progress and outcome. Given the current widespread use of epidural labor analgesia, relatively small effects on the progress and outcome of labor could have major public health consequences. Factors that produce dysfunctional labor increase labor pain. Retrospective studies show an association between the use of epidural analgesia and cesarean section. However, the highest quality evidence, randomized trials and impact studies, find no effect of epidural analgesia on the cesarean delivery rate. Epidural analgesia may influence the incidence of operative vaginal delivery. Epidural group patients in randomized trials have longer second-stage labors and receive more oxytocin than parenteral opioid group patients. First-stage labor tends to be longer in epidural group patients but the difference is not statistically significant. Theories for these labor speed differences abound. For unknown reasons, maternal hyperthermia is more common in epidural than in opioid group patients. Epidural analgesia has no negative impact on the delivery room condition of the neonate. Patients receiving epidural analgesia report better pain relief and more satisfaction than patients receiving opioid labor analgesia. Epidural analgesia may slow labor speed but has minimal effect on labor outcome.

Methadone and the hospice patient: prescribing trends in the home-care setting.

To identify frequency and utilization patterns of methadone by hospice patients in the home-care setting. All hospice patients admitted to a North American palliative care specialty pharmacy and dispensed methadone from November 1, 2001 to October 31, 2002 were analyzed. We also analyzed all hospice patients dispensed long-acting opioids during that same time period. A retrospective analysis of the pharmacy database was performed for patients dispensed methadone. Data was compared to the long acting opioid cohort to be able to identify any difference in terminal diagnoses present, and the presence of neuropathic pain in both groups. Methadone daily dosage was also analyzed during this study. Four hundred sixteen hospice patients were dispensed methadone over a twelve-month period of time. For comparison, 21,219 patients were prescribed a long-acting opioid preparation (sustained-release morphine, sustained-release oxycodone, or transdermal fentanyl). The most common terminal diagnosis for both groups was lung carcinoma. The distribution of terminal diagnoses was similar in both groups. The group prescribed methadone was found to have a higher incidence of neuropathic pain (30.5% of patients) when compared to the long-acting opioid group (16.9%). Most patients (61.3%) were prescribed daily methadone doses of 100 mg or less. Despite its potential clinical and economic benefits, methadone is not commonly prescribed for the hospice patient in the home-care setting. Clinicians may be more aware of the usefulness of methadone in the treatment of neuropathic pain.

Factors influencing constipation in advanced cancer patients: a prospective study of opioid dose, dantron dose and physical functioning.

The relationship between opioid dose, dantron dose, bowel function and physical functioning (measured with the modified Barthel Index) was determined in a sample of 50 inpatients with advanced cancer. Data were collected prospectively from chart review and patient interviews one week after admission to allow for protocol-driven management of constipation to be established. Bowel scores were significantly reduced in 35 patients treated with opioids compared with 15 patients not treated with opioids. Within the opioid group, however, there was no relationship between opioid dose, bowel score, dantron dose or Barthel Index. Higher doses of dantron were associated with better physical functioning (but not opioid dose) suggesting that for any given dose of opioid, fitter patients were treated with larger doses of laxatives. Factors other than opioid dose and physical functioning may be more important in contributing to constipation in this group of patients. Less potent opioid drugs, such as codeine, are just as likely to cause constipation as more potent opioids.

Remifentanil‐propofol vs. sufentanil‐propofol: optimal combinations in clinical anesthesia

Two opioid regimens, computer-simulated to provide optimal general anesthesia in combination with propofol, were compared using clinical criteria. Fifty patients undergoing thyroid surgery were blindly, prospectively and randomly allocated to receive either (a) i.v. remifentanil (1.5 micro g kg-1, followed by 0.2 micro g kg-1 min-1) or (b) i.v. sufentanil (0.2 micro g kg-1 followed by 0.2 micro g kg-1 h-1). Remifentanil infusion was stopped at the last skin suture. Sufentanil infusion was stopped 30 min before the end of surgery. Intravenous propofol was titrated to keep BIS at 50+/-5. Remifentanil and sufentanil groups were compared with regards to (a) propofol delivery, (b) hemodynamic and recovery variables, and (c) effect-site propofol levels during a steady-state period for effect-site remifentanil and sufentanil levels. P<0.05 was significant. Groups were similar in demographic data; types and durations of surgery; total propofol consumption; and response, extubation and emergence times. During the steady-state period for the opioid delivery, the remifentanil and sufentanil effect-site levels were 5.3 ng ml-1 and 0.18 ng ml-1, respectively (potency ratio=30). In both opioid groups, in accordance with previous computer-simulations, the effect-site propofol concentrations remained (a) within a narrow range unaffected by surgical stimuli, (b) significantly smaller in the remifentanil group than in the sufentanil group, but (c) smaller than expected from previous computer-simulations. More patients required ephedrine following induction of anesthesia in the remifentanil compared with the sufentanil group. The present clinical trial conducted in thyroid surgery is consistent with previous computer-simulated opioid-propofol combinations with respect to intraoperative and recovery variables. Effect-site propofol ranges were, however, lower than expected.

Associação de fentanil ou sufentanil à bupivacaína a 0,5% isobárica em raquianestesia: estudo comparativo

Since the discovery of opioid receptors and the increase in spinal cord neuropharma- cological knowledge as to transmission and inhibition of nociceptive stimulations, there has been an increased interest in spinal drugs for anesthesiology and pain relief. This study aimed at prospectively evaluating the clinical efficacy of fentanyl (25 microg) and sufentanil (5 microg) with isobaric bupivacaine (10 mg), in patients submitted to spinal anesthesia for varicose vein surgery. Participated in this study 60 patients, physical status ASA I and II, aged below 60 years, submitted to spinal anesthesia for varicose vein sugery, who were randomly distributed in three groups: B (10 mg isobaric bupivacaine), BF (10 mg isobaric bupivacaine and 25 microg fentanyl) and BS (10 mg isobaric bupivacaine and 5 microg sufentanil). Spinal anesthesia was induced in the left lateral position; lumbar puncture was performed at L3-L4, with 27G Quincke needles. The following parameters were evaluated after spinal anesthesia: onset time, sensory and motor block level. The following parameters were recorded during the procedure: arterial hypotension, bradycardia, respiratory depression, oxygen hemoglobin peripheral saturation decrease, nausea, vomiting, pruritus and shivering. Analgesia duration was evaluated in the post-operative period. Groups were homogeneous. There were no significant differences in onset time, motor block and analgesia duration. There were differences in sensory block level between the control group and the opioid groups in all studied moments. Pruritus was the most frequent side-effect in the opioid groups. The addition of fentanyl (25 microg) and sufentanil (5 microg) to isobaric bupivacaine (10 mg) in spinal anesthesia affects sensory block levels.

Comparison of intrathecal fentanyl and diamorphine in addition to bupivacaine for Caesarean section under spinal anaesthesia

Co-administration of small doses of opioids and bupivacaine for spinal anaesthesia reduces intraoperative discomfort and may reduce postoperative analgesic requirements in patients undergoing Caesarean section. Fentanyl and diamorphine are the two most frequently used agents in UK obstetric anaesthetic practice. Seventy-five healthy parturients scheduled for elective Caesarean section under spinal anaesthesia using hyperbaric 0.5% bupivacaine, were randomly allocated to additionally receive intrathecal fentanyl 20 micrograms, diamorphine 300 micrograms or 0.9% saline. Patients also received i.v. cyclizine and rectal diclofenac. Less supplementary intraoperative analgesia was required by patients in either opioid group (4%) compared with the control (32%) (P < 0.05). Twenty four hours after spinal injection, total mean (SD) postoperative morphine requirement was significantly lower if diamorphine was administered (31 (21) mg), in comparison with the other two groups (control 68 (26) mg; fentanyl 62 (26) mg) (P < 0.05). Reduced visual analogue pain scores were evident 12 h following diamorphine, but observed only for 1 h after fentanyl when compared with the control (P < 0.05). Mild pruritus was more common for 2 h after either spinal opioid (P < 0.05), but no inter-group differences were observed for the remainder of the first 24 h. Patients displayed deeper levels of sedation both acutely and 12 h after administration of intrathecal fentanyl (P < 0.05). Both intrathecal opioids reduce intraoperative discomfort, but only diamorphine reduced postoperative analgesic requirement beyond the immediate postoperative period.

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination Spinal Analgesic Chemotherapy: A Systematic Review

Combination spinal analgesic chemotherapy: a systematic review.

Combination spinal analgesic chemotherapy: a systematic review.

A comparison of the effectiveness of an opioid analgesic and a nonpharmacologic intervention to improve incentive spirometry volumes

The purpose of this study was to compare the effects of opioid analgesics and relaxation as interventions for incentive spirometry in postcardiovascular surgery patients. With the use of incentive spirometry change scores from pre- to posttreatment, 72 patients received either relaxation, opioid analgesia, or no intervention. Pre- to posttreatment differences in achieved spirometry volumes were significantly different for the 3 groups (F[2, 69] = 7.32; p =.002), whereas no difference in spirometry volume was found between the opioid and relaxation groups. Relaxation was as effective as opioid analgesia in permitting postcardiovascular surgical patients to deep breathe. © 2002 by the American Society of Pain Management Nurses

A family study of the high-risk children of opioid- and alcohol-dependent parents.

In this article, the author sought to use a high-risk study design focused on the children of parents with opioid or alcohol use disorders and children of parents with no substance use disorder (SUD) to evaluate the specificity of the risk conferred by the type of parental SUD. Using structured psychiatric interviews, cognitive assessments, and measures of social, academic, and family functioning, the authors studied 96 families (187 parents and 183 children, mean age of 11.6 years). Sixteen families had parental opioid dependence (22 children, 64% male), 14 families had parental alcohol dependence (22 children; 59% male), and 66 families had no SUD (controls; 139 children; 58% male). Fifty-nine percent of children of opioid-dependent parents had at least one major psychopathological condition, compared to 41% of the alcohol group and 28% of the control group (p < 0.01). The children of opioid- and alcohol-dependent parents were of lower socioeconomic status and had significantly more diffculties in academic, social, and family functioning than did controls. Children of opioid- and alcohol-dependent parents have significantly higher rates of psychopathology as well as more difficulties in academic, social, and family functioning compared to the children of non-SUD parents. In addition, notable trends emerged for the opioid group to have more psychopathology and functional impairment than the alcohol group. With a growing consensus that certain risk factors for later SUD start in childhood with potentially treatable childhood-onset disorders, new preventive approaches for individuals at risk may be developed targeting childhood precursors of

Intravenous ketorolac in the emergency department management of sickle cell pain and predictors of its effectiveness.

To evaluate the effectiveness of intravenous (IV) ketorolac tromethamine in the treatment of children with sickle cell disease with moderate to severe acute vaso-occlusive pain (VOP) and to develop a predictive model that would determine who would need additional IV analgesics. A prospective case series. The emergency department of an urban children's hospital in the southeastern United States. A convenience sample of 51 children aged 6 to 18 years, representing 70 distinct episodes of VOP requiring IV analgesics. All patients were given 0.5 to 1 mg/kg IV ketorolac and IV fluids. Patients, parents, nurses, and physicians assessed pain before and after ketorolac using a standard 100-mm visual analog scale (VAS). Of the 70 episodes of VOP, 37 (53%) adequately resolved with IV ketorolac and IV fluids and required no IV opioids (group A). Thirty-one episodes (47%) required the addition of an IV opioid (group B). Group B had a significantly greater proportion of episodes reporting 4 or more painful sites than group A, 43% (12/28) vs 9% (3/33), respectively (P<.01). Group B also had significantly higher mean initial VAS scores than group A as assessed by the patient (81 vs 60; P<.01), parent (71 vs 54; P<.01), nurse (78 vs 51, P<.01), and physician (69 vs 53; P =.01). Of the patient assessments with an initial VAS score greater than 70, 69% (18/26) required the addition of an opioid. First-line therapy with IV ketorolac and IV fluids resulted in adequate resolution of pain in 53% of episodes with acute VOP. A reported 4 or more painful sites and an initial VAS score greater than 70 were predictors of the likelihood to need additional IV analgesics.

Is epidural analgesia associated with an improved outcome following open Nissen fundoplication?

Postoperative epidural analgesia is increasingly popular in paediatric practice, although evidence of its benefit is scarce. We performed a retrospective analysis of a series of 104 consecutive open Nissen fundoplications, to determine whether mode of analgesia, epidural (n=65) or opioid infusion (n=39), influenced certain outcome measures, including intensive care utilization, duration of hospital stay, morbidity and mortality. The two groups were similar in terms of demographic characteristics and associated pathologies. Overall, morbidity and mortality (2%) rates were low. Mean duration of hospital stay was significantly greater for the opioid group, compared to those receiving epidural analgesia (13 vs. 8 days, P < 0.05). The number of patients who remained in hospital for more than 7 days was also significantly greater in the opioid group. Accepting the limitations of a retrospective study, these data suggest that epidural analgesia might be associated with an improved outcome following Nissen fundoplication and this merits a prospective study.

Pharmacology (81)

Endocrine consequences of long‐term intrathecal administration of opioids. (University of Antwerp, Edegem, Belgium) J Clin Endocrinol Metab 2000;85:2215–2222.This study involved 73 patients (29 men and 44 women) receiving opioids intrathecally for nonmalignant pain who were enrolled for extensive endocrine investigation. At the time of hormonal determination, the mean duration of opioid treatment was 26.6 ± 16.3 months; the mean daily dose of morphine was 4.8 ± 3.2 mg. The control group consisted of 20 patients (11 men and 9 women) with a comparable pain syndrome, but not treated with opioids. Decreased libido or impotency was present in 23 of 24 men receiving opioids. The serum testosterone level was below 9 nmol/L in 25 of 29 men and was significantly lower than that in the control group (P &lt; 0.001). The free androgen index was below normal in 18 of 29 men and was significantly lower than that in the control group (P &lt; 0.001). The serum LH level was less than 2 U/L in 20 of 29 men and was significantly lower than that in the control group (P &lt; 0.001). Serum FSH was comparable in both groups. Decreased libido was present in 22 of 32 women receiving opioids. All 21 premenopausal females developed either amenorrhea or an irregular menstrual cycle, with ovulation in only 1. Serum LH, estradiol, and progesterone levels were lower in the opioid group. In all 18 postmenopausal females significantly decreased serum LH (P &lt; 0.001) and FSH (P = 0.012) levels were found. The 24‐h urinary free cortisol excretion was below 20 μg/day in 14 of 71 opioid patients and was significantly lower than that in the control group (P = 0.003). The peak cortisol response to insulin‐induced hypoglycemia was below 180 μg/L in 9 of 61 opioid patients and was significantly lower than that in the nonopioid group (P = 0.002). The insulin‐like growth factor I sd score was below −2 sd in 12 of 73 opioid patients and was significantly lower than that in the control group (P = 0.002). The peak GH response to hypoglycemia was below 3 μg/L in 9 of 62 subjects and was significantly lower than that in the control group (P = 0.010). Thyroid function tests and PRL levels were considered normal. No metabolic disturbances were recorded, apart from significantly decreased high‐density lipoprotein cholesterol levels (P = 0.041) and elevated total/high density lipoprotein cholesterol ratio (P = 0.008) in the opioid group compared to the control group. Supplementation with gonadal steroids improved sexual function in most patients. Conclude of all patients receiving intrathecal opioids, the large majority of men and all women developed hypogonadotropic hypogonadism, about 15% developed central hypocorticism, and about 15% developed GH deficiency. These findings suggest that further investigations are required to determine the need for systematic endocrine work‐up in these patients and the necessity for substitutive therapy.

Respiratory effects of intraoperative alfentanil infusion in post-abdominal hysterectomy patients: A comparison of high versus low dose

Summary A number of reports have been published describing (recurrent) respiratory depression after the use of alfentanil intraoperatively. To evaluate the severity of respiratory depression after the administration of alfentanil, 49 patients undergoing general anaesthesia for abdominal hysterectomy were randomly allocated to one of three groups and studied in a double-blind manner. During surgery patients received no opioids (group 1), low dose (group 2) or high dose of alfentanil (group 3). Postoperatively patients were monitored with pulse oximetry and respiratory inductive plethysmography. Postoperative pain was managed with PCA morphine. Thirty-nine patients completed the study. Respiratory depressant effects were found in all three groups. A higher number of apnoeas (at 60 minutes in group 1: 3.3 ± 1.6; group 2: 3.5 ± 1.8; group 3: 12.2 ± 2.8) and a higher morphine consumption was found in group 2 when compared with group 1 and 3. No differences were found among the groups in the other respiratory parameters or in terms of the number of patients with respiratory depression at any one time. No cases of clear-cut recurrent respiratory depression were identified.

A Comparison of Remifentanil and Fentanyl in Patients Undergoing Surgery for Intracranial Mass Lesions

We compared the effects of remifentanil versus fentanyl during surgery for intracranial space-occupying lesions. Patients were randomly assigned to receive either remifentanil (0.5 microg. kg(-1). min(-1) IV during the induction of anesthesia reduced to 0.25 microg. kg(-1). min(-1) after endotracheal intubation; n = 49) or fentanyl (dose per usual practice of the anesthesiologist; n = 54). Anesthesia maintenance doses of isoflurane, nitrous oxide, and opioid were at the anesthesiologist's discretion for both groups. There were no differences between opioid groups for the frequency of responses (hemodynamic, movement, and tearing) to intubation, pinhead holder placement, skin incision, or closure of the surgical wound. Adverse event frequencies were similar between groups. Times to follow verbal commands (P < 0.001) and tracheal extubation (P = 0. 04) were more rapid for remifentanil. The percentage of patients with a normal recovery score (were alert or arousable to quiet voice, were oriented, were able to follow commands, had motor function unchanged from their preoperative evaluation, were not agitated, and had modified Aldrete Scores of 9-10) at 10 min after surgery was more for remifentanil (45% vs 18%; P = 0.005). By 20 min, no difference between groups existed (P = 0.27). Anesthesiologists used more isoflurane in the fentanyl group (4.22 vs 1.93 minimum alveolar anesthetic concentration hours). Neurosurgeons, blinded to treatment group, favored the use of remifentanil. Similar frequencies of light anesthesia responses and other adverse events suggest that intraoperative depths of anesthesia were similar in the two groups. Under these conditions, emergence was more rapid with remifentanil. This is consistent with the necessity for less isoflurane use in the remifentanil group and the intrinsic rapid clearance of this opioid. Patients given remifentanil-based anesthesia for craniotomy had faster recovery times from anesthesia than did those given fentanyl-based anesthesia.

Endocrine consequences of long-term intrathecal administration of opioids.

Intrathecal administration of opioids is a very efficient tool in the long-term control of intractable nonmalignant pain. However, despite the well known role of opioids in endocrine regulation, few data are available about possible effects on hypothalamic-pituitary function during this treatment. Seventy-three patients (29 men and 44 women; mean age, 49.2 +/- 11.7 yr) receiving opioids intrathecally for nonmalignant pain were enrolled for extensive endocrine investigation. At the time of hormonal determination, the mean duration of opioid treatment was 26.6 +/- 16.3 months; the mean daily dose of morphine was 4.8 +/- 3.2 mg. The control group consisted of 20 patients (11 men and 9 women; mean age, 54.2 +/- 14.0 yr) with a comparable pain syndrome but not treated with opioids. Decreased libido or impotency was present in 23 of 24 men receiving opioids. The serum testosterone level was below 9 nmol/L in 25 of 29 men and was significantly lower than that in the control group (P < 0.001). The free androgen index was below normal in 18 of 29 men and was significantly lower than that in the control group (P < 0.001). The serum LH level was less than 2 U/L in 20 of 29 men and was significantly lower than that in the control group (P < 0.001). Serum FSH was comparable in both groups. Decreased libido was present in 22 of 32 women receiving opioids. All 21 premenopausal females developed either amenorrhea or an irregular menstrual cycle, with ovulation in only 1. Serum LH, estradiol, and progesterone levels were lower in the opioid group. In all 18 postmenopausal females significantly decreased serum LH (P < 0.001) and FSH (P = 0.012) levels were found. The 24-h urinary free cortisol excretion was below 20 microg/day in 14 of 71 opioid patients and was significantly lower than that in the control group (P = 0.003). The peak cortisol response to insulin-induced hypoglycemia was below 180 microg/L in 9 of 61 opioid patients and was significantly lower than that in the nonopioid group (P = 0.002). The insulin-like growth factor I SD score was below -2 SD in 12 of 73 opioid patients and was significantly lower than that in the control group (P = 0.002). The peak GH response to hypoglycemia was below 3 microg/L in 9 of 62 subjects and was significantly lower than that in the control group (P = 0.010). Thyroid function tests and PRL levels were considered normal. No metabolic disturbances were recorded, apart from significantly decreased high density lipoprotein cholesterol levels (P = 0.041) and elevated total/high density lipoprotein cholesterol ratio (P = 0.008) in the opioid group compared to the control group. Supplementation with gonadal steroids improved sexual function in most patients. In conclusion, of all patients receiving intrathecal opioids, the large majority of men and all women developed hypogonadotropic hypogonadism, about 15% developed central hypocorticism, and about 15% developed GH deficiency. These findings suggest that further investigations are required to determine the need for systematic endocrine work-up in these patients and the necessity for substitutive therapy.

Effects of etonitazene consumption and abstinence on the signal transmission of μ-opioid receptors in brain membranes of rats

Rats, for 8 weeks consuming the μ-opioid agonist etonitazene (forced and free choice conditions yielding high and low drug-consumers), were sacrificed after 2 days or 6 weeks lasting drug deprivation. Binding characteristics of membranes from the parieto-occipital cortex of these four groups were compared with those of drug-naive controls. In all five groups, 1 μM of the μ-opioid receptor agonist [D–Ala2,N–MePhe4,Gly5–ol]enkephalin (DAMGO) increased the guanosine-5′-O-([35S]3-thio)triphosphate ([35S]GTPγS) binding activity on guanine nucleotide-binding (G) proteins, and 500nM of GTPγS decreased the [3H]DAMGO binding affinity. During acute withdrawal, both opioid consuming groups displayed a higher maximum efficacy (Emax) in basal [35S]GTPγS binding (34 and 31%, each P<0.01), but only the forced group showed a 58% higher net DAMGO-stimulated binding density Bmax (P<0.01) and 53% more activated G proteins per μ-opioid receptor (P<0.05). In the presence of GTPγS both groups revealed a higher affinity in [3H]DAMGO binding (each 25%, P<0.01). The long-term drug-deprived groups displayed no differences in their binding characteristics.

Controversies of Labor Epidural Analgesia

Controversies of Labor Epidural Analgesia

The naloxone eye‐drop test for opioid dependence

AbstractThe use of topical ophthalmic naloxone to detect physiological opioid dependence was tested in two double‐blind, placebo‐controlled trials a week apart. The subject group consisted of opioid‐dependent patients on methadone maintenance treatment. The control group consisted of medical student volunteers. For trial 1, two drops of naloxone hydrochloride (1 mg/ml) were instilled in one eye of both subjects and controls, while two drops of an inert saline solution were instilled into the opposite eye. For trial 2 the procedure was repeated. However, on this occasion all controls were administered a single subcutaneous injection of morphine sulphate. Pupil diameter following administration of naloxone was measured by photographs taken at 0, 60 and 90 minutes. Complete data for both days were obtained from 15 controls and 13 subjects. A significant difference was found between mean changes in pupil/iris ratio for the control group compared with the opioid group for both trials. However, discriminant analysis revealed that the test is likely to produce significant numbers of false positive and false negative results. In addition, the test precipitated an opiate withdrawal syndrome in many subjects, and bilateral mydriasis was evident in trial 2. The naloxone eye‐drop test does not appear to be a useful tool in determining the presence of neuroadaptation to opioids.