Hydromorphone Patient-controlled Analgesia Research Articles

Comparison of Analgesic Effects and Adverse Events of Hydromorphone PCIA Versus Sufentanil PCIA: A Retrospective Analysis

PurposeThe aim of this study was to compare the analgesic effect and adverse events of hydromorphone patient-controlled intravenous analgesia (PCIA) without background dose versus sufentanil PCIA with background dose in patients after surgery. DesignA retrospective analysis. MethodsFrom June 2020 to May 2021, 1594 eligible postoperative patients who received PCIA were collected in this study. According to the types of opioids, patients were divided into two groups: sufentanil group and hydromorphone group. Numerical Rating Scale (NRS), Functional Activity Scale (FAS) and Level of Sedation (LOS) were used to evaluate the analgesic effects between the two groups. In addition, total PCA use, effective number of PCA compressions, and adverse effects of PCIA were compared between the two groups. FindingsAt 24 hours (h) after sugery, the FAS score in the sufentanil group was higher than that in the hydromorphone group (P<0.05). Compared with the sufentanil group, total PCA use, total number of PCA compressions and effective number of PCA consumptions were significantly decreased in the hydromorphone group during a 48h period (P < 0.05). There were no statistical differences in NRS score, LOS score and adverse events between two groups at 24h and 48h after surgery. ConclusionsCompared with sufentanil PCIA with background dose, under the similar analgesic effect, hydromorphone PCIA without background dose provided lower PCA use. Our findings may provide useful evidence for more future studies related to postoperative analgesia.

Feasibility of hydromorphone PCA 10-day simple mode home management of patients in severe pain: A prospective multicenter study.

e24072 Background: Pain is a common symptom affecting patients with cancer. In clinical practice patients with advanced refractory cancer pain often face multiple anti-tumor treatments and prefer treatment at home or in community clinics versus hospitalization; thus, pain relief and drug management are challenging. Patient-controlled analgesia (PCA) is an essential component of analgesic treatment. However, difficulties associated with PCA configuration, unified pump configuration mode, and tube blockage may limit its use by both doctors and patients, negatively affecting large-scale promotion of PCA technology in hospitals and at home. In this study we optimized PCA parameters to resolve problems around cumbersome operation and tube blockage, thereby increasing pump utility and feasibility. We refer to this mode as the "10-day simple mode." The study objective is to evaluate the analgesic effect of the "10-day simple mode" of hydromorphone PCA and to explore its home-based convenience and use. Methods: A total of 100 patients with refractory cancer pain were included in this study. The pump configuration mode was divided into two stages. The first (titration) stage was: hydromorphone + normal saline with a total volume of 24 ml and pump speed of 1.0 ml/h. The second (maintenance) stage was: hydromorphone + normal saline with a total volume of 288 ml and pump speed of 1.2 ml/h with PCA of 2.4 ml. During the maintenance stage, if pain control was unsatisfactory the background dose was increased based on the number of PCA presses in the previous 24 hours. Patients' numeric rating scale (NRS) scores, quality of life scores, and adverse reactions were recorded before and after treatment. Results: Patients' average NRS score before treatment was 7.4 (7-10). Average time to successful titration was 49.6 minutes (35.6-56.9) and 40.7% of patients achieved successful titration within 30 minutes. After titration, the average NRS score was 3.2 (0-6). There was a statistically significant difference in NRS scores before and after titration (p &lt; 0.05). During maintenance, 56.0% of patients experienced breakthrough pain on day 1, when the average NRS score was 5.2. As background dosing continued breakthrough pain and average NRS score gradually decreased (p &lt; 0.05). Quality of life scores and patient satisfaction measured before and after 10 days of PCA pump use showed significant improvement (p &lt; 0.001). Conclusions: For patients with refractory cancer pain, the hydromorphone PCA "10-day simple mode" produces good analgesic effect, is easy to manage, and suitable for patients seeking home-based pain relief. These results warrant further clinical study. Clinical trial information: NCT05744089 .

Different doses of nalmefene combined with hydromorphone hydrochloride for postoperative analgesia after colorectal surgery: a randomized controlled study

BackgroundHydromorphone hydrochloride has a satisfactory postoperative analgesic effect for patients with colorectal cancer but is accompanied by a relatively high incidence of adverse events. Low-doses of naloxone combined with opioids for patient-controlled analgesia can reduce the incidence of drug-related adverse events. Nalmefene is a more selective opioid receptor antagonist than naloxone. The aim of this study was to determine the impact of low-doses of nalmefene on the analgesic effect and incidence of adverse events of patients with hydromorphone patient-controlled analgesia (PCA) undergoing colorectal radical surgery.MethodsNinety-nine patients undergoing elective laparoscopic or hand-assisted laparoscopic radical surgery under general anaesthesia were randomly divided into three groups. Group N1 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 2 µg/kg; Group N2 received hydromorphone hydrochloride 0.15 mg/kg + nalmefene 0.5 µg/kg; and the control group (Group C) received hydromorphone hydrochloride 0.15 mg/kg. All medications were diluted to 100 ml with normal saline. The primary outcome was pain intensity at 12 h after surgery; the secondary outcomes were the occurrence of nausea, vomiting and pruritus and the total analgesic consumption of the PCA pump at 1 h, 6 h, 12 h, 24 and 48 h after surgery.ResultsThe NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C (P = 0.025), and no difference was found between group N2 and group C (P > 0.05). Among the three groups, the NRS scores of Group N1 (2 µg/kg) were significantly lower than those of Group C at 12 h (P = 0.01) and 48 h (P = 0.01) postoperatively. Compared with 12 h postoperatively, the NRS scores were lower at 24 h postoperatively in Group N1 and Group C (P < 0.05) and significantly lower at 48 h postoperatively in all three groups (P < 0.001). There was a significant difference in the incidence of pruritus among the three groups (P = 0.036).ConclusionsNalmefene at a dosage of 2 µg/kg enhances the postoperative analgesic effect of hydromorphone hydrochloride and reduces the occurrence of postoperative pruritus.Trial RegistrationThe trial was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR2000033520, date: 03/06/2020).

Knowing the Dose to Control the Dose: Optimizing Patient-Controlled Analgesia in Adults with Sickle Cell Disease (SCD)

Introduction: Acute painful episodes are the most common cause of hospitalization in SCD. Intravenous (IV) opioids are the analgesic of choice to treat pain requiring hospitalization in adults. On-demand IV opioid dosing can be either via a patient-controlled analgesia (PCA) pump or via intermittent nurse bolus. Advantages of PCA include better analgesia accessibility and relative independence from staff. However, significant variability exists in PCA management. A multicenter, randomized-controlled trial of PCA strategies in SCD was terminated early due to slow accrual, stemming from barriers such as suboptimal communication between inpatient teams. Additional limitations with PCA include technological limitations and incomplete charting through a manual process. We initiated a quality improvement project to understand patterns of PCA use in patients hospitalized for SCD pain crises at our institution. Methods: We performed a retrospective manual chart review on all adult patients diagnosed with SCD pain crises admitted to the University of Cincinnati Medical Center (UCMC) from October 1 through December 31, 2022. Inpatient data collected included reason for admission, length of stay, and documentation of inpatient opioid usage in daily clinical notes. Hospitalizations requiring intensive care admission for severe complications were excluded. Outpatient data collected included demographics and outpatient opioid prescriptions via the state prescription drug monitoring database. The study was approved by the UCMC IRB. Results: Fifteen patients were admitted to UCMC a total of 24 times for SCD pain crises during the 3-month period. The patients ranged in age from 21 years to 73 years (median age 33 years, interquartile range (IQR) 19.5 years) and the majority (11/15) were women. Disease-modifying therapies prescribed included hydroxyurea (8/15, 53%), chronic transfusions (2/15, 13%), chronic transfusions plus hydroxyurea (1/15), voxelotor (1/15), no disease-modifying therapy (2/15). Nine patients were prescribed daily outpatient opioids that included an oral long-acting opioid plus an oral short-acting opioid. Out of the 24 hospitalizations, 11 were for an uncomplicated pain crisis, 10 were complicated by mild acute chest syndrome (mild hypoxia and/or abnormal chest imaging), and 3 patients experienced other treatable complications (2 with Staphylococcus epidermidis bacteremia, 1 with deep venous thrombosis). Five patients were admitted two or more times. Two patients, admitted a total of 5 times, were maintained on nurse-administered IV bolus opioids during their admissions, in addition to oral opioids. The remainder of the patients were treated with a hydromorphone PCA pump with on-demand bolus dosing only, in addition to home long-acting oral opioids when applicable. Two patients were ultimately transitioned from PCA onto nurse-administered bolus IV opioids, due to failure to achieve adequate analgesia with PCA. In 9 out of the 19 admissions using a PCA, daily MME or the equivalent was charted in at least one progress note (47%). The median LOS in the subgroup in which PCA use was charted at least once was 7 (IQR 3.5) days. In the 10 admissions on a PCA in which daily MME was never charted (53%), the median LOS was 11 (IQR 6.25) days. Among patients not receiving outpatient opioids, daily MMEs from the PCA in the first few days of hospitalization (when recorded) ranged from 24 to 520 (median 178, IQR 241) MME. In patients who had daily chronic pain on outpatient opioid therapy, daily inpatient MME from PCA ranged from 360 to 1020 (median 545, IQR 418) MME. In patients with multiple admissions during the study period, the recorded daily opioid use was about two times that in the single admission group (median 673, IQR 500 MME in the multiple admissions group; vs median 329, IQR 351 MME in the single admission group). Conclusions: Our data suggest that length of stay is shortened by ~4 days when clinicians quantify daily opioid use for patients on PCA. In addition, patients with frequent admissions tend to have higher inpatient daily opioid use. This hints that readmission may be partly driven by mild withdrawal when on outpatient opioids at lower MME. A major barrier to data collection was inconsistent documentation of daily opioid use. The next step in our quality improvement project is an educational curriculum on inpatient opioid management for residents and hospitalists.

Effects of Novel Multimodal Transversus Abdominis Plane Block on Postoperative Opioid Usage and Hospital Length of Stay Following Elective Ventral Hernia Repair.

Background and objective Traditional transversus abdominis plane (TAP) blocks consisting of a local anesthetic, typically bupivacaine, have previously been shown to reduce postoperative pain following gastrointestinal surgery, including hernia repair. However, elective abdominal wall reconstructions for the repair of large ventral hernias continue to cause patients significant postoperative pain, resulting in prolonged hospital stays and need for opioid pain medication. This study aimed to analyze the postoperative opioid pain medication usage and hospital length of stay (LOS) in patients who received a nontraditional multimodal TAP block of ropivacaine (local anesthetic), ketorolac (non-steroidal anti-inflammatory), and epinephrine following elective ventral hernia repair. Methods A retrospective review of medical records for patients who underwent elective robotic ventral hernia repair by a single surgeon was conducted. Postoperative hospital LOS and opioid usage for patients with the multimodal TAP block were compared to those without. Results A total of 334 patients met the inclusion criteria for LOS analysis: 235 received the TAP block and 109 did not. Patients who received the TAP block had a statistically significant shorter LOS compared to patients who had no TAP block (1.09 ± 1.22 days vs. 2.53 ± 1.57 days; P<0.001). Medical records for 281 patients, 214 with the TAP block and 67 without the TAP block, contained information and were analyzed for postoperative opioid usage. A statistically significantly fewer number of patients who had the TAP block required hydromorphone patient-controlled analgesia pump (3.3% vs. 36%; P<0.001) and oral opioids (29% vs. 78%; P<0.001) postoperatively. Those with TAP block required intravenous opioids more frequently (50% vs 10%; P<0.001) although at much less dosages than those without TAP block (4.86 ± 2.62 mg vs. 10.29 ±3.90 mg; P<0.001). Conclusion In conclusion, this multimodal TAP block of ropivacaine, ketorolac, and epinephrine may represents an effective method to improve hospital LOS and postoperative opioid usage in patients undergoing robotic abdominal wall reconstruction for ventral hernia repair.

Efficacy of patient-controlled hydromorphone analgesia in those undergoing uterine fibroid artery embolization via the right radial artery

ObjectiveTo evaluate the efficacy and safety of patient-controlled analgesia (PCA) with hydromorphone as perioperative analgesia during uterine artery embolization (UAE) via the right radial artery. Patients and methodsA total of 33 patients with uterine fibroids, who underwent UAE at the authors’ hospital between June 2021 and March 2022, were selected. Hydromorphone (10 ​mg) was dispensed into a 100 ​ml PCA pump with normal saline. Pump administration was initiated 15 ​min before the start of the procedure, and the intraoperative dose was adjusted according to patient pain level. A numerical rating scale was used to evaluate pain immediately after embolization, 5 ​min after embolization, at the end of the procedure, and 6, 12, 24, 48, and 72 ​h after the procedure. Side effects were also observed. ResultsThirty-three patients underwent uterine artery embolization via the right radial artery. Patient pain was well controlled at all time points surveyed, and patients reported satisfaction with analgesia. The median length of hospital stay was 5 days. There were 7 cases of adverse reactions, but no serious side effects were observed. ConclusionPatients reported positive experiences with arterial embolization of uterine fibroids via the right radial artery. Hydromorphone PCA effectively controlled pain. The PCA pump is easy to operate, has a low incidence of adverse reactions, and offers economic benefits at the patient and institutional levels.

Patient-Controlled Analgesia vs Intravenous Push Hydromorphone for Pain Management of Vaso-Occlusive Crisis Associated With Sickle Cell Disease

Patient-controlled analgesia (PCA) appears to be the preferred modality for treatment of pain associated with vaso-occlusive crisis (VOC) and is the current standard of therapy at most institutions. With limited data available, this study analyzed the effectiveness of PCA vs intravenous push (IVP) hydromorphone for pain management of VOC. The primary objective was to determine whether PCA or IVP hydromorphone is more effective in controlling VOC pain determined by a reduction in mean absolute difference pain intensity (MPI) from baseline to discharge. This retrospective single-center study evaluated differences in outcomes between patients treated with PCA vs those treated with IVP hydromorphone for VOC during hospital admission. Those 18 years or older admitted with one of the following International Classification of Diseases, Tenth Revision codes were included: D57.0 (Hb-SS disease with crisis), D57.2 (sickle cell/Hb-C disease), and D57.4 (sickle cell thalassemia), and administered PCA or IVP hydromorphone. The observed difference in absolute pain scores were not statistically significant (p = 0.753). The use of IVP hydromorphone resulted in a significant reduction in length of stay (LOS) and morphine milligram equivalent (MME) use compared to PCA, but was associated with a numerical increase in treatment failures. This study was limited by its retrospective nature, uneven distribution of groups, and only reviewed use of IVP and PCA hydromorphone at one institution.

Safety and efficacy of intravenous hydromorphone patient-controlled analgesia versus intramuscular pethidine in acute pancreatitis: An open-label, randomized controlled trial.

Background: Hydromorphone patient-controlled analgesia (PCA) provides satisfactory postoperative pain therapy, but its effect has not been assessed in acute pancreatitis (AP). Aim: To assess the safety and efficacy of intravenous hydromorphone PCA for pain relief in AP. Methods: This open-label trial included AP patients admitted within 72 h of symptom onset, aged 18–70 years old, and with Visual Analog Scale (VAS) for pain intensity ≥5. They were randomized to receive intravenous hydromorphone PCA (0.05 mg/h with 0.2 mg on-demand) or intramuscular pethidine (50 mg as required) for three consecutive days. Intramuscular dezocine (5 mg on demand) was the rescue analgesia. The primary outcome was the change of VAS score recorded every 4 h for 3 days. Interim analysis was conducted by an Independent Data and Safety Monitoring Committee (IDSMC). Results: From 26 July 2019 to 15 January 2020, 77 patients were eligible for the intention-to-treat analysis in the interim analysis (39 in the hydromorphone group and 38 in the pethidine group). Baseline parameters were comparable between groups. No difference in VAS between the two groups was found. Hydromorphone PCA was associated with higher moderately severe to severe cases (82.1% vs. 55.3%, p = 0.011), acute peripancreatic fluid collections (53.9% vs. 28.9%, p = 0.027), more cumulative opioid consumption (median 46.7 vs. 5 mg, p < 0.001), higher analgesia costs (median 85.5 vs. 0.5 $, p < 0.001) and hospitalization costs (median 3,778 vs. 2,273 $, p = 0.007), and more adverse events (20.5% vs. 2.6%, p = 0.087). The per-protocol analysis did not change the results. Although a sample size of 122 patients was planned, the IDSMC halted further recruitment as disease worsening or worse clinical outcomes between the groups in the interim analysis. Conclusion: Hydromorphone PCA was not superior to pethidine in relieving pain in AP patients and might have worse clinical outcomes. Therefore, its use is not recommended. Clinical Trial Registration: Chictr.org.cn. ChiCTR1900025971

Narcotic waste in the operating room and immediately post operatively in gynecologic oncology surgery (118)

Narcotic waste in the operating room and immediately post operatively in gynecologic oncology surgery (118)

Scheduled methadone reduces overall opioid requirements after pediatric posterior spinal fusion: A single center retrospective case series.

Posterior spinal fusion to correct adolescent idiopathic scoliosis is associated with significant postoperative pain. Different modalities have been reported as part of a multimodal analgesic plan. Intravenous methadone acts as a mu-opioid agonist and N-Methyl-D-aspartate (NMDA) antagonist and has been shown to have opioid-sparing effects. Our multimodal approach has included hydromorphone patient-controlled analgesia (PCA) with and without preincisional methadone, and recently postoperative methadone without a PCA. We hypothesized that a protocol including scheduled postoperative methadone doses would reduce opioid usage compared to PCA-based strategy. A retrospective chart review of patients undergoing posterior spinal fusion for adolescent idiopathic scoliosis between 2015 and 2020 was performed. There were three patient groups: Group PCA received a hydromorphone PCA without methadone; Group PCA + Methadone received preincisional methadone and a hydromorphone PCA; Group Methadone received preincisional methadone, scheduled postoperative methadone, and no PCA. The primary outcome was postoperative opioid use over 72 h. Secondary outcomes included pain scores, sedation scores, and length of stay. Group PCA (n=26) consumed 0.33 mg/kg (95% CI [0.28, 0.38]) total hydromorphone equivalents, Group PCA + methadone (n=39) 0.30 mg/kg (95% CI [0.25, 0.36]) total hydromorphone equivalents, and Group methadone (n=22) 0.18 mg/kg (95% CI [0.15, 0.21]) total hydromorphone equivalents (p=.00096). There were no statistically significant differences between the groups for secondary outcomes. A protocol with intraoperative and scheduled postoperative methadone doses resulted in a 45% reduction in opioid usage compared to a PCA-based protocol with similar analgesia after pediatric posterior spinal fusion.

198. Rapid recovery pathway (RRP) utilizing intrathecal morphine decreases overall hospital costs and improves quality of care in adolescent idiopathic scoliosis (AIS)

<h3>BACKGROUND CONTEXT</h3> Posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is a complex procedure for which charges can exceed $150,000. Among the total costs, inpatient and intensive unit care contributed 22%. Many institutions have implemented rapid recovery pathways (RRP) to improve patient care following scoliosis surgery. Most RRPs encourage early ambulation, feeding, and stooling in combination with patient-controlled analgesia (PCA). <h3>PURPOSE</h3> This study aims to determine the effects of a multimodal RRP, utilizing intrathecal morphine (ITM) in combination with oral pain medication, on hospital costs and patient management. <h3>STUDY DESIGN/SETTING</h3> Retrospective review. <h3>PATIENT SAMPLE</h3> AIS patients undergoing posterior spinal fusion between 2013 and 2019. <h3>OUTCOME MEASURES</h3> Surgical outcomes and associated costs. <h3>METHODS</h3> Patients after February 2018 were placed in the RRP group. These patients received ITM as part of their multimodal analgesia. Fusion level-matched control patients, treated before February 2018, received hydromorphone PCA as the mainstay of their postoperative pain management. At discharge PCA patients received 14-day prescriptions for oxycodone compared to 7-day prescriptions in the ITM group. Perioperative data, requests for opioid refill, and overall costs were compared using McNemar's and Wilcoxon Signed-Rank tests. <h3>RESULTS</h3> A total of 363 patients were included (PCA: 255, RRP/ITM: 108). BMI (p = 0.786) and median preoperative Cobb angle (p = 0.343) were similar between both groups. RRP patients had a significantly shorter length of stay (3 days vs 5 days, p <0.001) and 65.2% of RRP patients ambulated by postoperative day (POD) 1 compared to 43.4% of PCA patients (p < 0.001). The fraction of patients who requested opioid refills was similar between both groups (p = 0.082). The cost of intraoperative anesthesia was significantly higher for RRP patients ($2,286.87 v $1,958.70, p<0.001). Perioperative hospital stay ($39,990.00 vs $55,680.00, p<0.001) was significantly lower for the RRP patients. Due to different prescription durations, the cost of home opioid medications was $98.94 for PCA patients vs $56.28 for RRP, based on standard Medicaid costs. <h3>CONCLUSIONS</h3> The RRP protocol following PSF had lower total hospital costs and lower home opioid requirements after surgery than the traditional PCA protocol. <h3>FDA DEVICE/DRUG STATUS</h3> intrathecal morphine, oxycodone: Approved.

Intravenous patient-controlled analgesia hydromorphone combined with pregabalin for the treatment of postherpetic neuralgia: a multicenter, randomized controlled study.

BackgroundPostherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. Despite the effectiveness of anticonvulsants, antidepressants, and lidocaine patches in reducing PHN, many patients still face intractable pain disorders. In this randomized controlled study, we evaluated whether hydromorphone through intravenous patient-controlled analgesia (IV PCA) was effective in relieving PHN.MethodsPatients with PHN were randomly divided into two groups, one group received oral pregabalin with IV normal saline, another group received oral pregabalin with additional IV PCA hydromorphone for two weeks. Efficacy was evaluated at 1, 4, and 12 weeks after the end of the treatments.ResultsTwo hundred and one patients were followed up for 12 weeks. After treatment, numerical rating scale (NRS) score of patients in the hydromorphone group was significantly lower than that of the control group, and the difference of NRS scores between the two groups was statistically significant at 4 and 12 weeks after treatment. The frequency of breakthrough pain in the hydromorphone group was significantly lower than that in the control group 1 and 4 weeks after treatment. After treatment, the quality of sleep in the hydromorphone group was significantly improved compared with the control group. The most common adverse reactions in the hydromorphone group were dizziness and nausea, with no significant respiratory depression.ConclusionsIV PCA hydromorphone combined with oral pregabalin provides superior pain relief in patients with PHN, which is worthy of clinical application and promotion.

Reducing Opioid Dependence and Improving Patient Experience for Living Kidney Donors with Transversus Abdominis Plane Block

Rapid recovery after laparoscopic living donor nephrectomy (LLDN) for kidney donation is highly desirable for living kidney donors. To uphold rapid recovery, good analgesia with minimal adverse effects, including those related to opioid dependence, is essential. A pre-operative transversus abdominis plane (TAP) block with liposomal bupivacaine can effectively aid in perioperative pain management, while reducing opioid requirements. We conducted a single-center retrospective study involving patients 18 years and older who underwent LLDN to determine whether a TAP block with liposomal bupivacaine is efficacious in pain management after LLDN, while reducing opioid use. The study group comprised of patients who received a preoperative TAP block with liposomal bupivacaine in place of hydromorphone patient-controlled analgesia (PCA) and the control group included patients who received hydromorphone PCA post-operatively. Both groups were supplemented with oral and intravenous analgesics for breakthrough pain, as needed. The primary endpoint was reduction in post-operative opioid use in morphine milligram equivalents (MME). Secondary endpoints included: post-operative pain scores, postoperative length of stay, and re-hospitalizations within 7 days of discharge. Sixty-six patients were included in our study, with 33 in each group. Patients in both groups were well matched demographically. The study group who received TAP block demonstrated a significant reduction in post-operative opioid use (92.05 MME vs. 53.98 MME, p &lt; 0.05) when compared to the control group who received hydromorphone PCA. Both groups achieved similar analgesia with comparable pain scores. There was no difference between postoperative hospital lengths of stay for both groups. Two patients in the control group were re-admitted due to small bowel obstruction within seven days of discharge. In conclusion, TAP block with liposomal bupivacaine significantly reduced postoperative opioid use, while also proving to be safe, efficacious and feasible in patients undergoing LLDN.

Hydromorphone population pharmacokinetics in pediatric surgical patients.

Hydromorphone is an opioid agonist used for pediatric analgesia. Due to lack of data, pediatric dosing (based on adult pharmacokinetic models) is not optimal. This study characterizes hydromorphone population pharmacokinetics in pediatric surgical patients. In this prospective observational study, 34 children (4-18years, bodyweight 23-89.6kg) received multiple intravenous hydromorphone boluses followed by postoperative hydromorphone patient-controlled analgesia. Arterial blood samples were collected before and at 3, 10, 30, and 90 (and few samples at 1350) minutes after the first dose. Hydromorphone concentrations were measured by validated LC-MS/MS assay. Nonlinear mixed-effects modeling was used for pharmacokinetic model development. The final population pharmacokinetic model was evaluated by visual predictive check and bootstrap analysis. Monte Carlo simulations based on the final pharmacokinetic model determined optimal patient-controlled analgesia parameters to achieve a target of 20ng/mL (as the median effective analgesic concentration), using minimum effective analgesic concentration of 4ng/mL as a proxy for patient-controlled analgesia dose demand, and not exceeding the defined safe upper threshold of 40ng/mL. Hydromorphone pharmacokinetic profiles were adequately described by a two-compartmental model with first-order elimination. Bodyweight was found to be a significant covariate for hydromorphone clearance. Allometrically scaledpharmacokinetic parameter estimates (per 70kg), systemic clearance (0.748L/min), volume of distribution (33L), peripheral clearance (1.57L/min), and peripheral volume of distribution (146L) were similar to reported adult parameter estimates. Sex, race, age, and type of surgery were not identified as significant covariates. To identify optimal patient-controlled analgesia dosing parameters, we simulated several initial loading doses, demand doses, and lockout intervals. Our simulations support an initial patient-controlled analgesia loading dose of 15µg/kg followed by a demand dose of 6µg/kg with lockout intervals of 20minutes. After intravenous hydromorphone, plasma pharmacokinetic profiles in children undergoing different surgeries were well described by a two-compartment population allometric pharmacokinetic model using bodyweight as the size descriptor. Model informed simulations identified patient-controlled analgesia parameters to inform initial settings, with adjustments as needed based on observed individual effects.

Low-dose ketamine infusion reduces postoperative hydromorphone requirements in opioid-tolerant patients following spinal fusion: A randomised controlled trial.

The current opioid epidemic highlights the urgent need for effective adjuvant therapies to complement postoperative opioid analgesia. Intra-operative ketamine infusion has been shown to reduce postoperative opioid consumption and improve pain control in opioid-tolerant patients after spinal fusion surgery. Its efficacy for opioid-naïve patients, however, remains controversial. We hypothesised that low-dose ketamine infusion after major spinal surgery reduces opioid requirements in opioid-tolerant patients, but not in opioid-naïve patients. Randomised placebo-controlled study. Single-centre, tertiary care hospital, November 2012 until November 2014. A total of 129 patients were classified as either opioid-tolerant (daily use of opioid medications during 2 weeks preceding the surgery) or opioid-naïve group, then randomised to receive either ketamine or placebo; there were thus four groups of patients. All patients received intravenous hydromorphone patient-controlled analgesia postoperatively. Patients in the ketamine groups received a ketamine infusion (bolus 0.2 mg kg over 30 min followed by 0.12 mg kg h for 24 h). Patients in the placebo groups received 0.9% saline. The primary outcome was opioid consumption during the first 24 h postoperatively. The secondary outcome was numerical pain scores during the first 24 h and central nervous system side effects. Postoperative hydromorphone consumption was significantly reduced in the opioid-tolerant ketamine group, compared with the opioid-tolerant placebo group [0.007 (95% CI 0.006 to 0.008) versus 0.011 (95% CI 0.010 to 0.011) mg kg h, Bonferroni corrected P < 0.001]. There was no difference in hydromorphone use between the opioid-naïve groups (0.004 and 0.005 mg kg h in the opioid-naïve ketamine and placebo group, respectively, P = 0.118). Pain scores did not differ significantly between the opioid-tolerant ketamine group and the opioid-naïve groups. There was no significant difference in side effects among groups. Postoperative low-dose ketamine infusion reduces opioid requirements for the first 24 h following spinal fusion surgery in opioid-tolerant, but not in opioid-naïve patients. NCT03274453 with clinicaltrials.gov.

Ketamine versus hydromorphone patient-controlled analgesia for acute pain in trauma patients

BackgroundIt is unknown whether ketamine administered via patient-controlled analgesia (PCA) provides adequate analgesia while reducing opioid consumption in the traumatically injured patient. Differences in opioid consumption, pain scores, and adverse effects between ketamine and hydromorphone PCA were studied. Materials and methodsThis is an investigator-initiated, single-center, double-blinded, randomized, pilot trial conducted from 2014 to 2016 at a level 1 trauma center. Nonintubated trauma patients in intensive care, who were receiving PCA, were randomized to ketamine or hydromorphone PCA plus opioid analgesics for breakthrough pain. ResultsTwenty subjects were randomized. There was no difference in median daily breakthrough opioid use (10 [0.63-19.38] mg versus 10 [4.38-22.5] mg, P = 0.55). Subjects in the ketamine group had lower median cumulative opioid use on therapy day 1 than the hydromorphone group (4.6 [2.5-15] mg versus 41.8 [31.8-50] mg, P < 0.001), as well as in the first 48 h (10 [3.3-15] mg versus 48.5 [32.1-67.5] mg, P < 0.001) and first 72 h (10 [4.2-15] mg versus 42.5 [31.7-65.2] mg, P < 0.001) of therapy. Daily oxygen supplementation requirements were lower in the ketamine group (0.5 [0-1.5] L/min versus 2 [0.5-3] L/min, P = 0.020). Hallucinations occurred more frequently in the ketamine group (40% versus 0%, P = 0.090). ConclusionsKetamine PCA led to lower cumulative opioid consumption and lower oxygen supplementation requirements, though hallucinations occurred more frequently with use of ketamine. Additional studies are needed to investigate the tolerability of ketamine as an alternative to traditional opioid-based PCA.

Epidurals in Pancreatic Resection Outcomes (E-PRO) study: protocol for a randomised controlled trial

IntroductionEpidural analgesia provides an important synergistic method of pain control. In addition to reducing perioperative opioid consumption, the deliverance of analgesia into the epidural space, effectively creating a sympathetic blockade,...

Pregabalin Did Not Improve Pain Management After Spinal Fusions.

The treatment of postoperative pain is a challenge after posterior spinal fusions. Pain management using predominantly opioids is often associated with multiple adverse effects, while multimodal postoperative analgesia may provide adequate pain relief with fewer opioid side effects. The purpose of this review is to determine whether addition of 150 mg pregabalin daily would reduce narcotic requirements and improve outcomes after posterior lumbar fusion (PLF). The method used is a randomized, controlled trial of elective PLF patients who received pregabalin or placebo. With institutional review board (IRB) approval, 86 patients undergoing elective posterior lumbar fusion, ASA I-III, were randomized to receive either a placebo or pregabalin after obtaining written informed consent. Both arms, i.e., placebo and pregabalin, consisted of 43 patients each.The 86 patients for elective PLF were randomly assigned to receive 150mg of pregabalin 1h before surgery and then 150mg daily, or a placebo tablet. All patients received a similar general anesthetic and in the post-anesthesia care unit (PACU), started on intravenous (IV) patient-controlled analgesia (PCA) of hydromorphone (0.2mg/ml). Postoperative pain was assessed daily until discharge using a Numerical Rating Scale (NRS) at rest and with physical therapy (PT). Patients were also assessed twice daily for level of sedation and nausea and/or vomiting and expected PT milestones. All narcotics (IV, oral) were documented. Demographics and operative time between groups were similar. PCA hydromorphone administration and oral narcotic intake were not statistically different between the two groups. However, an increased incidence of nausea and vomiting in the placebo group reached statistical significance (p<0.05). In addition, there was no statistical difference between groups with respect to achieving PT milestones and hospital discharge day. After PLF, patients receiving pregabalin 150mg/day did not have reduced IV narcotic usage, improved PT milestones, or reduced length of hospital stay. We were unable to demonstrate an analgesic advantage to prescribing pregabalin to patients undergoing lumbar spinal fusions.

Randomised, double-blind, parallel group, placebo-controlled study to evaluate the analgesic efficacy and safety of VVZ-149 injections for postoperative pain following laparoscopic colorectal surgery

IntroductionIn spite of advances in understanding and technology, postoperative pain remains poorly treated for a significant number of patients. In colorectal surgery, the need for developing novel analgesics is especially...

Narcotic-only Epidural Infusion for Posterior Spinal Fusion Patients: A Single-Center, Retrospective Review.

Adequate and safe postoperative analgesia for patients with idiopathic scoliosis undergoing posterior spinal fusion (PSF) remains challenging and controversial. A past adverse event in this patient population triggered a change of our institution's practice from epidurals containing bupivacaine and has resulted in use of epidurals containing solely narcotic (hydromorphone) for postoperative analgesia. This retrospective review looks at our experiences with hydromorphone patient-controlled epidural analgesia for postoperative analgesia in this patient population. Electronic medical records of all children with a diagnosis of idiopathic scoliosis who underwent PSF surgery at our institution during the period of January 2011 to October 2011 were reviewed from the time they entered the PACU through the first 72 hours following PACU discharge. Specifically, the charts were reviewed for pain scores, sedation scores, narcotic use, use of adjuvant medications, antiemetics, antipruritics, hours to first ambulation, hours to first oral intake, respiratory rate, SpO2 values, need for any respiratory interventions, length of stay, and any adverse events. Fifty-six patients were enrolled. Three patients had their epidurals removed within the first 24 hours (5.4% failure rate). Highest mean pain scores ranged from 5.6±2.3 to 5.8±2.2 with median pain scores ranging from 4 to 6. There were no respiratory or neurological adverse events. Ambulation occurred on either postoperative day 1 or 2. The incidence of vomiting in this study was 34% in the first 24 hours post-PACU discharge and during this period, 61% of patients received ondansetron, for either nausea or pruritus. The mean length of stay for our patients was 3.95 days, with a median of 4 days. This retrospective review suggests that hydromorphone epidurals used for pain control in postoperative PSF patients are a reasonable alternative to IV-PCA, in terms of analgesia, side-effect profile, and length of stay. Level III-retrospective study.