Post-operative opioid-related adverse events with intravenous oxycodone compared to morphine: A randomized controlled trial.

BACKGROUND: The value of intravenous oxycodone compared to morphine remains controversial. The purpose of this trial was to compare opioid-related adverse events (ORAES) of intravenous oxycodone and morphine after total hip arthroplasty. METHODS: Patients scheduled for total hip arthroplasty were enrolled in this study of post-operative pain treatment with intravenous oxycodone or intravenous morphine (ratio 1:1). After surgery, patients received similar drug regimens for titration in the post-operative care unit followed by intravenous patient-controlled analgesia (PCA). The primary outcome was the number of patients with ≥1 ORAEs within the first 24 hours defined as either nausea, vomiting, respiratory depression, pruritus, urinary retention requiring evacuation, allergy, hallucinations. Secondary outcomes included pain scores and opioid consumption. RESULTS: The analysis included 238 patients with similar characteristics. There were 55 patients with at least one ORAEs in the oxycodone group vs 46 in the morphine group: 48% vs 40%, P = .19; relative risk = 1.22 (0.91:1.63). Intravenous oxycodone vs intravenous morphine requirements were respectively (median, IQR): 6 (0-11) vs 8 (0-12) mg (P = .06) for titration, 15 (8-26) vs 8 (5-16) mg (P = .001) for PCA, and 22 (12-37) mg vs 19 (11-28) mg for cumulated intravenous consumption (P = .048). During the first 24 hours, there was no difference in secondary outcomes (oxycodone vs morphine, respectively, in %): nausea (15 vs 13), vomiting (5 vs 5), urinary retention (20 vs 12) or pain scores. CONCLUSION: This study demonstrates that IV oxycodone did not significantly reduce ORAEs within the first 24 hours compared to similar ratio of IV morphine.

Multimodal oral analgesia strategy after ambulatory arthroscopic shoulder surgery: case series using adaptive therapeutic approaches by sequential analysis.

BACKGROUND: Pain control and quality of recovery (QoR) at home remains a challenge after ambulatory shoulder arthroscopy. This study aims to assess the QoR and pain relief using a sequential implementation strategy for rescue analgesic drugs. METHODS: After institutional review board approval, patients (>18 years, American Society of Anesthesiology [ASA] score 1-3 stable) scheduled for ambulatory surgery under general anesthesia with a single-shot interscalene nerve block were enrolled. After discharge, patients received standard information regarding the postoperative recovery and care consisting of a multimodal analgesic regime (acetaminophen and ketoprofen for 5 days). The first 48 postoperative hours allowed us to compare 3 different rescue drug regimes with a control group, in sequential order: tramadol (control group), tramadol + nefopam, immediate-release oxycodone (IR), and extended-release oxycodone (ER). The primary endpoint was the QoR 40 score at 48 hours after surgery. Secondary endpoints were pain relief and adverse events over a 7-day period. An intention-to-treat statistical analysis was performed with sequential analysis (as an interim analysis) every 20 patients. Results were recorded as medians and interquartiles (25-75). RESULTS: We analyzed 109 patients with similar characteristics among groups. The QoR 40 scores were similar for the tramadol group (168 [161-172]), the tramadol + nefopam group (161 [151-173], P = .09), and the IR group (164 [153-169], P = .17), but higher for the ER group (176 [167-181], P = .03). Concerning adverse events, drugs were interrupted more frequently in the tramadol + nefopam group (36 %). In the ER group, a higher quality of postoperative relief was attained in the domains of pain and sleep. CONCLUSION: The present study shows that a combination of IR and ER oxycodone over a short period of time (<48 hours) is associated with a better QoR at home after ambulatory shoulder surgery.

A comparison of the pharmacodynamics and pharmacokinetics of bupivacaine, ropivacaine (with epinephrine) and their equal volume mixtures with lidocaine used for femoral and sciatic nerve blocks: a double-blind randomized study.

BACKGROUND: Mixtures of lidocaine with a long-acting local anesthetic are commonly used for peripheral nerve block. Few data are available regarding the safety, efficacy, or pharmacokinetics of mixtures of local anesthetics. In the current study, we compared the effects of bupivacaine 0.5% or ropivacaine 0.75% alone or in a mixed solution of equal volumes of bupivacaine 0.5% and lidocaine 2% or ropivacaine 0.75% and lidocaine 2% for surgery after femoral-sciatic peripheral nerve block. The primary end point was onset time. METHODS: In a double-blind, randomized study, 82 adults scheduled for lower limb surgery received a sciatic (20 mL) and femoral (20 mL) peripheral nerve block with 0.5% bupivacaine (200 mg), a mixture of 0.5% bupivacaine 20 mL (100 mg) with 2% lidocaine (400 mg), 0.75% ropivacaine (300 mg) or a mixture of 0.75% ropivacaine 20 mL (150 mg) with 2% lidocaine (400 mg). Each solution contained epinephrine 1:200,000. Times to perform blocks, onset times (end of injection to complete sensory and motor block), duration of sensory and motor block, and morphine consumption via IV patient-controlled analgesia were compared. Venous blood samples of 5 mL were collected for determination of drug concentration at 0, 5, 15, 30, 45, 60, and 90 min after placement of the block. RESULTS: Patient demographics and surgical times were similar for all four groups. Sciatic onset times (sensory and motor block) were reduced by combining lidocaine with the long-acting local anesthetic. The onset of bupivacaine-lidocaine was 16 +/- 9 min versus 28 +/- 12 min for bupivacaine alone. The onset of ropivacaine-lidocaine was 16 +/- 12 min versus 23 +/- 12 for ropivacaine alone. Sensory blocks were complete for all patients within 40 min for those receiving bupivacaine-lidocaine versus 60 min for those receiving bupivacaine alone and 30 min for those receiving ropivacaine-lidocaine versus 40 min for those receiving ropivacaine alone (P < 0.05). Duration of sensory and motor block was significantly shorter in mixture groups. There was no difference among groups for visual analog scale pain scores and morphine consumption during the 48 h postoperative period, except for bupivacaine alone (median: 9 mg) versus bupivacaine-lidocaine mixture (15 mg), P < 0.01. There was no difference in the incidence of adverse events among groups. Plasma concentrations of bupivacaine and ropivacaine were higher, and remained elevated longer, in patients who received only the long-acting local anesthetic compared to patients who received the mixture of long-acting local anesthetic with lidocaine (P < 0.01). CONCLUSION: Mixtures of long-acting local anesthetics with lidocaine induced faster onset blocks of decreased duration. Whether there is a safety benefit is unclear, as the benefit of a decreased concentration of long-acting local anesthetic may be offset by the presence of a significant plasma concentration of lidocaine.

Comparison of axillary nerve block duration using mepivacaine in non-insulin diabetic or renal insufficiency patients: a controlled observational matched multicenter trial.

BACKGROUND: Although studies in diabetic patients demonstrated delayed recovery after long-acting local anesthetic, its effects with short-acting LA remains to be determined. Using mepivacaine, the authors evaluated the duration of axillary nerve blocks in diabetic (DP), renal failure (creatinine clearance <30 mL.min-1) (RP) and healthy patients (HP). METHODS: We prospectively included consecutive patients aged 18-80 years, with DP (N.=37), RP (N.=32) and HP (N.=48) scheduled for distal upper limb surgery. Before surgery, an axillary nerve block (20 mL mepivacaine 15 mg.mL-1) was performed with an ultrasound approach combined with nerve stimulation. Five mL was injected for each nerve: median, ulnar, radial, musculocutaneous nerves. The primary endpoint measured was the duration of sensory block. For statistical analysis, each HP patient was matched with RP and DP patient (1:1), with regards to age (range±5 years) and sex. RESULTS: Patient characteristics were similar between groups. Creatinine clearance was 14±8 mL.min-1 in RP group and HbA1c (%) was 7.5±1.5 in DP group. Mean duration of diabetic or renal insufficiency illness were respectively eight and 12 years. Onset time for sensory and motor blocks were similar between groups. Average time for sensory block duration was similar between DP vs. HP (235±52 vs. 230±54 min, P=0.71); and between RP vs. HP (234±51 vs. 229±57 min, P=0.65). CONCLUSIONS: The short-acting LA (mepivacaine) are associated with similar pharmacodynamic effects in diabetic and renal failure patients as compared with healthy patients.

Comparison of 3 intensities of stimulation threshold for brachial plexus blocks at the midhumeral level: a prospective, double-blind, randomized study.

BACKGROUND: We conducted this prospective randomized study to compare the success rate and the onset time between 3 intensities of stimulation threshold (<0.5, 0.5-0.64, and 0.65-0.8 mA) when using a peripheral nerve stimulation at the midhumeral level. METHODS: Sixty-nine adult patients undergoing elective hand surgery were studied. Blocks were performed using conventional nerve stimulation technique. Needle advance began at 2 mA (1 Hz, 0.1 millisecond). When motor response (MR) occurred at less than 0.5 mA, needle position was fixed for "group <0.5 mA." For "group 0.5-0.64 mA," the needle was withdrawn until MR occurred at greater than 0.5 mA and disappeared at less than 0.5 mA. For "group >0.65 mA," the needle was withdrawn until MR occurred at greater than 0.65 mA and disappeared at less than 0.65 mA. For each group, patients received 8 mL of ropivacaine 7.5 mg/mL on the 4 nerves (radial, median, ulnar, and musculocutaneous). Primary end point was the number of failed radial nerve sensory blocks at 30 mins. RESULTS: The time to perform the block was not different between the 3 groups (17 mins [SD, 7 mins] vs 13 mins [SD, 8 mins] and 13 mins [SD, 4 mins], respectively). The time required to obtain a complete sensory block was shorter for the 4 nerves in group <0.5 mA, with a statistical significance for radial and musculocutaneous nerves in group <0.5 mA versus group 0.5-0.64 mA and group >0.65 mA. Patients in group <0.5 mA had a greater success rate for complete sensory radial nerve compared with those of group 0.5-0.64 mA and group >0.65 mA at any interval times between 5 and 30 mins (P = 0.0001). Supplemental local anesthesia was provided for the 3 groups more frequently for the median nerve, with no difference between groups. Group >0.65 mA required 5 general anesthesias (20%) as compared with 1 (4%) in group <0.5 mA (P < 0.05). No adverse event (dysesthesia) occurred after 48 hrs and 45 days. CONCLUSION: We conclude that intensity of stimulation influenced onset time and success rate.

Spinal anesthesia-induced hypotension: a risk comparison between patients with severe preeclampsia and healthy women undergoing preterm cesarean delivery.

We previously showed that, in comparison with term healthy parturients, patients with severe preeclampsia had a less frequent incidence of spinal hypotension, which was less severe and required less ephedrine. In the present study, we hypothesized that these findings were attributable to preeclampsia-associated factors rather than to a smaller uterine mass. The incidence and severity of hypotension were compared between severe preeclamptics (n = 65) and parturients with preterm pregnancies (n = 71), undergoing spinal anesthesia for cesarean delivery (0.5% bupivacaine, sufentanil, morphine). Hypotension was defined as the need for ephedrine (systolic blood pressure <100 mm Hg in parturients with preterm fetuses or 30% decrease in mean blood pressure in both groups). Apgar scores and umbilical arterial blood pH were also studied. Neonatal and placental weights were similar between the groups. Hypotension was less frequent in preeclamptic patients than in women with preterm pregnancies (24.6% versus 40.8%, respectively, P = 0.044). Although the magnitude of the decrease in systolic, diastolic, and mean arterial blood pressure was similar between groups, preeclamptic patients required less ephedrine than women in the preterm group to restore blood pressure to baseline levels (9.8 +/- 4.6 mg versus 15.8 +/- 6.2 mg, respectively, P = 0.031). The risk of hypotension in the preeclamptic group was almost 2 times less than that in the preterm group (relative risk = 0.603; 95% confidence interval, 0.362-1.003; P = 0.044). The impact of Apgar scores was minor, and umbilical arterial blood pH was not affected. We conclude that preeclampsia-associated factors, rather than a smaller uterine mass, account for the infrequent incidence of spinal hypotension in preeclamptic patients.

Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison.

In this prospective cohort study, we compared the incidence and severity of spinal anesthesia (SA)-associated hypotension in severely preeclamptic (n = 30) versus healthy (n = 30) parturients undergoing cesarean delivery. After the administration of IV fluids, SA was performed with hyperbaric 0.5% bupivacaine, sufentanil, and morphine. Blood pressure (BP) was recorded before and at 2-min intervals for 30 min after SA. Clinically significant hypotension was defined as the need for ephedrine (systolic BP decrease to <100 mm Hg in healthy parturients or 30% decrease in mean BP in both groups). Despite receiving a smaller fluid volume (1653 +/- 331 mL versus 1895 +/- 150 mL; P = 0.005) and a larger bupivacaine dose (10.5 +/- 0.9 mg versus 10.0 +/- 0.7 mg; P = 0.019), the severely preeclamptic patients had a less frequent incidence of clinically significant hypotension (16.6% versus 53.3%; P = 0.006), which was less severe and required less ephedrine. The risk of hypotension was almost six times less in severely preeclamptic patients (odds ratio, 0.17; 95% confidence interval, 0.05-0.58; P = 0.006) than that in healthy patients.