Timing Of Opioid Administration Research Articles

Incidence and risk factors for delirium after open heart surgery with cardiopulmonary bypass

Background & objectives: Postoperative delirium is a prevalent complication, particularly following cardiac surgery, and has detrimental effects on patient outcomes, including increased morbidity and mortality and prolonged stays in the intensive care unit. This study aims to estimate the incidence and identify the risk factors for delirium.
 Methodology: This prospective observational study was conducted on adult patients undergoing open-heart surgery with cardiopulmonary bypass at the Cardiovascular Surgery Unit at Bachmai Hospital, Vietnam. The Confusion Assessment Method for the ICU (CAM-ICU) was utilized to assess delirium twice daily during the initial four days post-surgery. Perioperative variables were analyzed by univariable and multivariable logistic regression.
 Results: Among the 285 patients included in this study, 56 were diagnosed with delirium using the CAM-ICU, representing a prevalence rate of 19.6%. Multivariate regression analysis revealed several independent risk factors for delirium, including advanced age (odd ratio - OR; 95% confidence interval-CI) (1.07; 1.03-1.10), a history of cerebrovascular accident (3.95; 1.31-11.84), prolonged cardiopulmonary bypass duration (1.02; 1.00-1.03), postoperative atrial fibrillation (2.47; 1.15-5.28), and opioid use time (13.65; 5.69-32.75).
 Conclusion: The incidence of delirium after open heart surgery with cardiopulmonary bypass was 19.6%. Advanced age and a history of cerebrovascular accidents were identified as non-modifiable risk factors for postoperative delirium. Meanwhile, there were three modifiable risk factors, including cardiopulmonary bypass duration, atrial fibrillation, and the time of opioid administration.
 Abbreviations: CAM-ICU: Confusion Assessment Method for the Intensive Care Unit
 Key words: Postoperative Delirium; Risk Factors; Incidence; Open-Heart Surgery; Cardiac Surgery
 Citation: Nguyen TT, Ta DD, Ho HS, Duong HD. Incidence and risk factors for delirium after open heart surgery with cardiopulmonary bypass. Anaesth. pain intensive care 2023;27(6):639−645; DOI: 10.35975/apic.v27i6.2354
 Received: Oct 04, 2023; Revised: Oct 28, 2023; Accepted: Oct 31, 2023

37 Procedural Pain Management in Burn Patients (Phase II) - A Quality Improvement Project

IntroductionThis quality improvement project (QI) focused on reducing procedural pain. Phase I of this project demonstrated a need to improve our patients' and nurses’ satisfaction with pain control management during hydrotherapy. In this phase (Phase II), we educated the nursing staff on 1) appropriate dosing and timing of opioid administration (Oral and IV) and 2) need for more frequent midazolam administration before hydrotherapy. We also assessed the safety and potential benefits of ketamine for procedural pain control.MethodsPatients undergoing wound cleaning procedures were surveyed for up to three hydrotherapy encounters. Nurses were educated on procedural pain control prior to this current phase. A convenience sample of patients underwent ketamine administration. Ketamine was administered per protocol starting at 0.3 or 0.4 mg/kg with intermittent boluses of 0.25 mg/kg as needed. Demographics, opioid (oral morphine equivalents, OME), midazolam, and ketamine doses and time of administration, and adverse events were collected. Patient pain scores (1-10) before and after hydrotherapy and patient and nurse satisfaction scores (1-10) after hydrotherapy were collected. Paired t-tests and one-way ANOVA were performed. P < 0.05 was considered significant.ResultsDuring Phase II, 9 patients and 19 encounters were analyzed; of which ketamine was administered for 10 events. Compared to Phase I (28 Patients and 50 encounters), education of the nursing staff resulted in a significant improvement in giving midazolam prior to hydrotherapy (78.9% vs. 10%; p < 0.001) and opioid administration (27.4 OME vs. 20.2 OME, p = 0.043). Timing of opioid administration did not improve when compared to Phase I (Outside the window of efficacy: 42.1% vs. 43.8%, p = 0.903). Both patient (8.7 ± 2.4 vs. 7.7 ± 2.1; p = 0.011) and nurse (8.2 ± 2.1 vs. 7.3 ± 1.9; p = 0.021) satisfaction scores regarding pain control improved. None of the patients who received ketamine experienced adverse effects. Notably, the use of ketamine improved nurse satisfaction scores with patient pain control (9.2 ± 0.8 vs. 7.1 ± 2.6; p = 0.035). While patients on ketamine were more satisfied with pain control, significance was not reached (9.4 ± 1.1 vs. 7.9 ± 3.2; p = 0.315).ConclusionsOur data demonstrate that nurse education regarding medication administration was effective, but further education is needed to improve the timing of opioid administration. Ketamine offers additional benefits that deserve additional study.

Comparison of impact of adjuvant treatment of midazolam, fentanyl, and magnesium sulfate with intrathecal bupivacaine on block characteristics and postoperative analgesia in knee arthroplasty: A randomized clinical trial

Objective: To compare the efficacy of midazolam, fentanyl, and magnesium sulfate as adjuvants to intrathecal bupivacaine on both block characteristics and postoperative analgesia in knee arthroplasty.Methods: This randomized double-blind clinical trial recruited spinal anesthesia patients of the American Society of Anesthesiologists class I or II, who needed knee arthroplasty. Patients were stratified into three intervention groups, including the midazolam group, the fentanyl group, and the magnesium sulfate group, and the patients were administered with midazolam, fentanyl, and magnesium sulfate, respectively. Hemodynamic parameters, sensory and motor block, and pain score (Visual Analogue Scale) were measured and compared among the three groups.Results: A total of 105 patients were included in this study with 35 patients in each group. There was no statistically significant difference in terms of oxygen saturation, mean blood pressure, duration of surgery, and postoperative complications, including nausea, vomiting, bradycardia, dizziness, and hypotension, as well as the time of opioid administration among the three groups (P>0.05). Statistically significant differences were found in terms of heart rate at 15, 30, 45, 60, 75, and 105 min after beginning of operation among the three groups, which was lower in the midazolam group (P<0.05). The midazolam group showed a shorter time to achieve sensory block after spinal anesthesia, sensory block to T8 or higher and sensory block to T12 and L1 (P<0.05). Besides, the three groups showed significantly differences in terms of onset of motor block after spinal anesthesia and time to achieve motor block to T8 or higher or Bromage score 3 (P=0.001). No significant difference was noted in pain scores among the three groups (P>0.05).Conclusion: Midazolam resulted in a shorter time to achieve sensory and motor block to T8 or higher, the onset of motor block and sensory block after spinal anesthesia, and time to achieve sensory block to T12 and L1, and the pain scores were not significantly different among the groups. Thus, midazolam can be highly underlined, if a shorter onset of sensory and motor blocks is targeted. [Funded by the research deputy of Arak University of Medical Sciences (No.99258); fa.irct.ir number, IRCT20141209020258N164].

Impact of Timing of Preprocedural Opioids on Adverse Events in Procedural Sedation.

The risk of respiratory depression is increased when opioids are added to sedative agents. In our recent multicenter emergency department (ED) procedural sedation cohort, we reported a strong association between preprocedural opioids and sedation-related adverse events. We sought to examine the association between timing of opioids and the incidence of adverse sedation outcomes. We conducted a secondary analysis of a prospective cohort of children aged 0 to 18years who received sedation for a painful procedure in six Canadian pediatric EDs from July 2010 to February 2015. The primary risk factor was timing of opioid administration, adjusted for age, opioid type, preprocedural and sedation medications, and procedure type. Outcomes were 1) oxygen desaturation, 2) vomiting, and 3) positive pressure ventilation (PPV). Of the 6,295 children in the original cohort, 1,806 (29%) received a preprocedural opioid. Patients receiving preprocedural opioids had a higher incidence of oxygen desaturation (risk difference= 4.3%, 95% confidence interval [CI]= 2.9% to 5.8%), vomiting (risk difference2.0%, 95% CI= 0.7% to 3.3%), and PPV (risk difference= 1.5%, 95% CI= 0.7% to 2.3%). Multivariable regression with timing of opioids modeled as a restricted cubic spline revealed the risk for each outcome was highest when opioids were administered in the 30minutes prior to sedation. Timing of opioid administration was statistically significantly associated with oxygen desaturation and vomiting (p<0.0001) but not with PPV (p=0.113). Timing of opioids was significantly associated with the risk of oxygen desaturation and vomiting. Being aware of this increased risk will help clinicians prepare for sedation and the potential need for patient rescue.

Antenatal interventions based upon fetal surveillance of the daily opioid-exposed fetus: a descriptive analysis

Objective: Daily opioid dependence for maternal pain management, methadone maintenance, or buprenorphine/naloxone therapy is an increasing trend in modern obstetrics. Opioids may produce depressive effects on fetal neurobehavioral status and thus on fetal heart rate patterns. Our primary objective was to describe the current methods utilized in antenatal monitoring of the daily opioid exposed fetus; and to describe interventions based upon monitoring which precipitated a recommendation for delivery. Our ultimate goal was to determine an optimal, evidence-based recommendation for fetal assessment of the daily opioid exposed pregnancy.Study design: A retrospective review of patients undergoing antenatal assessment from January 2016 through April 2017 at two maternal–fetal medicine testing centers identified singleton, fetuses without a known major genetic abnormality with daily opioid exposure. Nonstress tests, amniotic fluid indexes, biophysical profiles, umbilical artery Doppler measurements, and serial biometry were analyzed. Test characteristics and frequency of interventions for abnormal monitoring were quantified.Results: Criteria for daily opioid exposure was identified in 27 patients (77.8% on methadone (n = 21), 14.8% on prescription opioid for chronic pain (n = 4), and 7.4% on buprenorphine/naloxone (n = 2)). Mean maternal age was 30.3 years ±5.5 (range 21–42 years). Parity zero was 6/27 (22.2%). Identified race was 52% Caucasian, 26% African American, 19% Hispanic, and 4% Pacific Islander. There were 112 growth scans, 102 biophysical profiles, 10 isolated nonstress tests, and 81 umbilical artery Doppler studies reviewed. Delivery precipitated by abnormal testing occurred in 6/27 patients (22.2%). Gestational ages of delivery were all between 36 and 38 weeks. Indications for delivery were isolated oligohydramnios 2/6 (one at 37 weeks, one at 38 weeks), oligohydramnios with associated intrauterine growth restriction 2/6 (both at 36 weeks), isolated nonreactive nonstress test 1/6 (occurring at 38 weeks), and low biophysical profile score 1/6 (occurring at 36 weeks). The average nonstress test baseline was 131 (±11) beats per minute (range of 120–150), with no episodes of significant fetal bradycardia or tachycardia. Overall, 94.6% (106/112) of the nonstress tests were reactive, all nonstress tests had variability, 96.4% (108/112) had moderate variability, and 99.1% (111/112) had no decelerations. Time to nonstress test reactivity was <20 min in 93% (104/112), with a mean time to first acceleration of 5.3 (±7.7) min (range of 1–44). Umbilical artery Doppler measurements had an elevated systolic to diastolic ratio >95% for gestational age in 9/83 cases, with no measurements demonstrating absent or reversed end diastolic flow. Umbilical artery Doppler studies did not initiate changes in management.Conclusion: In our population, antepartum assessment with a biophysical profile at no later than 36-week gestation identified all fetuses with testing abnormalities necessitating delivery in the daily opioid exposed fetus (6/27, 22.2%). Oligohydramnios was the most frequent indication for delivery. Serial growth ultrasounds by 32 weeks were necessary to identify the 11.1% of growth restricted, opioid exposed fetuses. A depressive effect of daily opioids on nonstress test reactivity or variability was not evident in our cohort. Future studies should attempt to define optimal monitoring based upon category of opioid dependence, type and dose of opioid consumed, and timing of opioid administration.

Stroke outcome after domiciliary use of opioids in the peri-stroke period.

Background:Stroke affects large number of people worldwide resulting in disability. The people in the northern region of India follow some domiciliary practices, which include administration of opioids at the onset of stroke to retard its progression.Aim:To study the effect of opioids on the outcome and severity of stroke when used as domiciliary treatment in peri-stroke period.Materials and Methods:A prospective, observational study on stroke patients was carried out in Department of Neurology, Dayanand Medical College and Hospital, Ludhiana, Punjab, India from March 2012 to March 2013. Data were collected in a semi-structured proforma. The variables which were studied included socio-demographic characteristics such as age, gender, religion, socio-economic status, and place of inhabitation. The time of opioid administration, approximate amount administered, frequency of administration, duration of hospital stay, risk factors and co-morbid conditions were also studied. The stroke severity was analyzed by comparing National Institutes of Health Stroke Scale (NIHSS) score and outcome by comparing Modified Rankin Scale (MRS) score in both the groups at the time of admission and at the time of discharge.Results:Out of n = 100 recruited patients, n = 44 (Group A) reported opioid intake in the peri-stroke period and n = 56 (Group B) did not. Proportions of patients from rural areas were 61.4% in Group A and 37.5% in Group B. Mean age in groups A and B was 63 ± 9.15 and 59.8 ± 13.87 years, respectively; in these groups male proportions were 70.5% and 60.7%, respectively. At admission, mean NIHSS scores in Groups A and B were 10.0 ± 4.48 and 10.8 ± 4.51, respectively; on discharge, these scores were 6.3 ± 3.83 and 7.7 ± 3.79, respectively. At admission, mean MRS scores in Groups A and B were 3.7 ± 1.14 and 3.8 ± 1.32, respectively; upon discharge, these scores were 2.8 ± 1.18, 3.1 ± 1.23 respectively.Conclusion:In this cohort, we found that the domiciliary practice of opioids administration in the peri-stroke period is more common among the elderly and in the rural areas. There was no statistically significant difference in the mean NIHSS and MRS scores at admission as well as discharge implying that the opioid administration did not improve outcome or decrease the severity of the stroke. Our findings are robust enough to propose a larger sample size and follow-up in future studies to definitively ascertain the effect of opioids as pretreatment in stroke patients.

Postoperative patients’ perspectives on rating pain: A qualitative study

BackgroundIn postoperative pain treatment patients are asked to rate their pain experience on a single uni-dimensional pain scale. Such pain scores are also used as indicator to assess the quality of pain treatment. However, patients may differ in how they interpret the Numeric Rating Scale (NRS) score. ObjectivesThis study examines how patients assign a number to their currently experienced postoperative pain and which considerations influence this process. MethodsA qualitative approach according to grounded theory was used. Twenty-seven patients were interviewed one day after surgery. ResultsThree main themes emerged that influenced the Numeric Rating Scale scores (0–10) that patients actually reported to professionals: score-related factors, intrapersonal factors, and the anticipated consequences of a given pain score. Anticipated consequences were analgesic administration—which could be desired or undesired—and possible judgements by professionals. We also propose a conceptual model for the relationship between factors that influence the pain rating process. Based on patients’ score-related and intrapersonal factors, a preliminary pain score was “internally” set. Before reporting the pain score to the healthcare professional, patients considered the anticipated consequences (i.e., expected judgements by professionals and anticipation of analgesic administration) of current Numeric Rating Scale scores. ConclusionsThis study provides insight into the process of how patients translate their current postoperative pain into a numeric rating score. The proposed model may help professionals to understand the factors that influence a given Numeric Rating Scale score and suggest the most appropriate questions for clarification. In this way, patients and professionals may arrive at a shared understanding of the pain score, resulting in a tailored decision regarding the most appropriate treatment of current postoperative pain, particularly the dosing and timing of opioid administration.

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Timing of Opioid Administration as a Quality Indicator for Pain Crises in Sickle Cell Disease

Timing of opioid administration as a quality indicator for pain crises in sickle cell disease.

Time to opioid administration (TTO) has been suggested as a quality of care measure for sickle cell disease patients with vaso-occlusive crisis (VOC). We sought to determine whether TTO was associated with outcomes of emergency department (ED) visits for VOC. We conducted a single-center retrospective cohort study of ED visits for VOC. The primary outcome was hospital admission, with secondary outcomes of change between the first 2 pain scores, area under the curve (AUC) for pain scores at 4 hours (pain score AUC), total ED length of stay, and total intravenous opioids. In both univariate and multivariate analyses, mixed regression (logistic for admission, linear for secondary outcome variables) was used to evaluate association of TTO with outcome. In 177 subjects, 414 ED visits for VOC were identified. Inpatient admission occurred in 53% of visits. The median TTO for admitted patients was 86 minutes vs 87 minutes for those not admitted. TTO was not associated with inpatient admission in either univariate or multivariate analyses. In multivariate analyses with secondary outcomes, decreased TTO was associated with greater improvement between the first 2 pain scores, decreased pain score AUC, decreased total ED length of stay, and increased total opioids. Although TTO was not associated with admission, it was independently associated with 4 important secondary outcomes: change in initial pain scores, pain score AUC, total ED length of stay, and total intravenous opioids. The association of a process measure, TTO, with these outcomes encourages the institution of TTO reduction efforts in the ED.

Intravenous opioid dosing and outcomes in emergency patients: a prospective cohort analysis

Objectives Pain management in emergency department (ED) patients is variable and often inadequate. This study sought to (1) describe the variability in intravenous opioid dosing and (2) compare the outcomes that result from the most commonly prescribed opioid doses. Methods This prospective cohort study enrolled emergency patients who were prescribed intravenous morphine or hydromorphone as their initial analgesic. Subjects were interviewed at the time of opioid administration and 1 to 2 hours after opioid administration. Outcomes included the numeric pain score change (using a 0-10 scale), the proportion achieving a 50% pain score reduction, and the proportion developing side effects. Logistic regression was used to assess the effects of demographic, clinical, and treatment variables on outcomes. Results Six hundred ninety-one patients were analyzed. Initial equianalgesic dosages varied by a factor of 27 (from 1 mg morphine to 4 mg hydromorphone). Opioid dose titration occurred in only 21% of patients. Outcomes were similar across the range of opioid dosages before and after adjusting for potentially confounding variables. Among patients not taking opioids at home who received a total of 4 mg of morphine or less. 48% achieved at least a 50% pain score reduction and 60% did not want additional analgesics. Conclusions We found marked opioid dosing variability and infrequent opioid dose titration. A substantial number of ED patients with severe pain responded well to relatively low opioid dosages. Improved ability to predict opioid dose requirements and strategies that increase the use of opioid dose titration in ED patients are needed.

Outcomes After Intravenous Opioids in Emergency Patients: A Prospective Cohort Analysis

Pain management continues to be suboptimal in emergency departments (EDs). Several studies have documented failures in the processes of care, such as whether opioid analgesics were given. The objectives of this study were to measure the outcomes following administration of intravenous (IV) opioids and to identify clinical factors that may predict poor analgesic outcomes in these patients. In this prospective cohort study, emergency patients were enrolled if they were prescribed IV morphine or hydromorphone (the most commonly used IV opioids in the study hospital) as their initial analgesic. Patients were surveyed at the time of opioid administration and 1 to 2 hours after the initial opioid dosage. They scored their pain using a verbal 0-10 pain scale. The following binary analgesic variables were primarily used to identify patients with poor analgesic outcomes: 1) a pain score reduction of less than 50%, 2) a postanalgesic pain score of 7 or greater (using the 0-10 numeric rating scale), and 3) the development of opioid-related side effects. Logistic regression analyses were used to study the effects of demographic, clinical, and treatment covariates on the outcome variables. A total of 2,414 were approached for enrollment, of whom 1,312 were ineligible (658 were identified more than 2 hours after IV opioid was administered and 341 received another analgesic before or with the IV opioid) and 369 declined to consent. A total of 691 patients with a median baseline pain score of 9 were included in the final analyses. Following treatment, 57% of the cohort failed to achieve a 50% pain score reduction, 36% had a pain score of 7 or greater, 48% wanted additional analgesics, and 23% developed opioid-related side effects. In the logistic regression analyses, the factors associated with poor analgesia (both <50% pain score reduction and postanalgesic pain score of >or=7) were the use of long-acting opioids at home, administration of additional analgesics, provider concern for drug-seeking behavior, and older age. An initial pain score of 10 was also strongly associated with a postanalgesic pain score of >or=7. African American patients who were not taking opioids at home were less likely to achieve a 50% pain score reduction than other patients, despite receiving similar initial and total equianalgesic dosages. None of the variables we assessed were significantly associated with the development of opioid-related side effects. Poor analgesic outcomes were common in this cohort of ED patients prescribed IV opioids. Patients taking long-acting opioids, those thought to be drug-seeking, older patients, those with an initial pain score of 10, and possibly African American patients are at especially high risk of poor analgesia following IV opioid administration.

Preemptive Opioid Analgesia Does Not Influence Pain After Abdominal Hysterectomy

Opioid administration before surgical stimulus may reduce or prevent subsequent pain. We studiied the effect of timing of opioid administration on the pain-related behaviour after abdominal hysterectomy. Eighty-five patients scheduled for abdominal hysterectomy were blindly randomized to receive fentanyl 10 μg· kg−1 before induction of anaesthesia (FA), after peritoneal incision (FB) or after removal of the uterus (FC), or sufentanil 1 μg· kg−1 before induction of anaesthesia (SA) or after peritoneal incision (SB) respectively. All patients received a standard postoperative analgesic regimen. The time from skin closure to the first analgesic request was recorded. Pain was assessed using the VAS and a verbal rating score (VSR 1 =no pain to 6 = intolerable pain) every 30 min until patients asked for the first analgesic, and 24 hr postoperatively. The times from skin closure to the first analgesic request did not differ among the five groups. The VAS scores using the two-way ANOVA with repeated measurements differed among the five groups (F = 4.046, df = 4, 213, P < 0.005). The VAS scores with one-way ANOVA differed among the five groups 30 min postoperatively (F = 4.542, df = 4, 58, P < 0.003), being higher in the FA (6.5 ± 1.8) and SA (5.9 ± 2.1) groups than in the FC (3.2 ± 2.5) group, and at 120 min postoperatively (F = 3.217, df= 4, 18, P < 0.05), being higher in the FA than in the FB group (6.1 ± 7.5 and 2.6 ± 1.9 respectively). The VRS scores did not differ among the FA, FB, FC, SA and SB groups at any time. This study failed to demonstrate a preemptive effect of systemic administration of fentanyl or sufentanil in the doses tested.

Factors influencing the immunomodulating effect of met-enkephalin: Role of mitogen dose, stage of cell activation, and time of opioid administration

Met-enkephalin in a concentration range of 10−15 to 10−9 M exhibited an immunomodulating effect upon concanavalin A-induced proliferation of mouse lymphocytesin vitro. The effect of met-enkephalin was shown to depend on the stage of lymphocyte activation, the time of opioid administration, and the dose of mitogen. Met-enkephalin produced the maximal effect when given in the phases of increase or decrease of the proliferative response. Met-enkephalin augmented the proliferative response to the suboptimal dose of concanavalin A and, on the contrary, inhibited the response to the optimal dose of mitogen. Administration of met-enkephalin at different times could both inhibit and stimulate proliferation depending on the stage of lymphocyte activation. An inhibitory effect was induced by δ-class opioid ligand, while κ-ligand was responsible for stimulation. Naloxone abolished the stimulating effect of opioids.

The Timing of Opioid Administration in Postdural Puncture Headache

The Timing of Opioid Administration in Postdural Puncture Headache