Evaluation of a clinical protocol using intranasal fentanyl for treatment of vaso-occlusive crisis in sickle cell patients in the emergency department

Background Vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visits and admission in children with sickle cell disease (SCD). Objectives This study aims to evaluate whether the use of a new pain management pathway using intranasal (IN) fentanyl from triage leads to improved care, translated by a decrease in time to first opiate dose. Methods We performed a retrospective chart review of patients with SCD who presented to the emergency department (ED) with VOC, in the period pre- (52 patients) and post- (44 patients) implementation period of the protocol. Time to first opiate was the primary outcome and was evaluated pre- and postimplementation. Patients received a first opiate dose within 52.3 minutes of registration (interquantile range [IQR] 30.6, 74.6), corresponding to a 41.4-minute reduction in the opiate administration time (95% confidence interval [CI] −56.1, −27.9). There was also a 43% increase in the number of patients treated with a nonintravenous (IV) opiate as first opiate dose (95% CI 26, 57). In patients who were discharged from the ED, there was a 49% decrease in the number of IV line insertions (95% CI −67, −22). There was no difference in the hospitalization rates (difference of 6 [95% CI −13, 25]). Conclusions This study validates the use of our protocol using IN fentanyl as first treatment of VOC in the ED by significantly reducing the time to first opiate dose and the number of IVs.

Perioperative Intravenous Acetaminophen in Pediatric Tonsillectomies

Purpose: This study investigated the effect of perioperative intravenous (IV) acetaminophen on opioid requirements in pediatric patients undergoing tonsillectomy at a single center. Methods: This retrospective chart review included patients who were less than 18 years old and underwent an outpatient tonsillectomy procedure. Patients who received non–Food and Drug Administration (FDA)-approved dosing of IV acetaminophen, without documented weights, and on chronic pain medications at the time of the procedure were excluded. The primary outcome was opioid requirements postoperatively prior to discharge measured as morphine equivalents per kilogram. Descriptive statistics were used to compare differences between groups. A multivariate analysis was performed, accounting for differences between groups in baseline and procedural characteristics. Results: In total, 157 patients were included in this study, of whom 55 had received IV acetaminophen and 102 had not. The average IV acetaminophen dose for was 14.5 mg/kg for patients weighing less than 50 kg (n = 22); the remaining patients received the maximum 1 g dose. Patients who received IV acetaminophen were less likely to be administered postoperative opiates as compared with those did not (45.5% vs 63.7%, odds ratio = 0.48, P = .036). There was a trend toward a decrease in total amount of opiates administered with IV acetaminophen (0 vs 0.033 µg/kg, P = .61). After adjusting for age and documented pain assessment, IV acetaminophen administration remained a significant factor for postoperative opiate administration. Conclusions: Perioperative administration of IV acetaminophen was associated with less frequent administration of symptom-directed opiates in pediatric tonsillectomies. This finding indicates that the agent may have an opioid-sparing effect in this patient population.

The Effect of Chronic Morphine or Methadone Exposure and Withdrawal on Clock Gene Expression in the Rat Suprachiasmatic Nucleus and AA-NAT Activity in the Pineal Gland

The circadian rhythms of many behavioral and physiological functions are regulated by the major circadian pacemaker in the suprachiasmatic nucleus. Long-term opiate addiction and drug withdrawal may affect circadian rhythmicity of various hormones or the sleep/activity pattern of many experimental subjects; however, limited research has been done on the long-term effects of sustained opiate administration on the intrinsic rhythmicity in the suprachiasmatic nucleus and pineal gland. Here we compared the effects of repeated daily treatment of rats with morphine or methadone and subsequent naloxone-precipitated withdrawal on the expression of the Per1, Per2, and Avp mRNAs in the suprachiasmatic nucleus and on arylalkylamine N-acetyltransferase activity in the pineal gland. We revealed that 10-day administration and withdrawal of both these drugs failed to affect clock genes and Avp expression in the SCN. Our results indicate that opioid-induced changes in behavioral and physiological rhythms originate in brain structures downstream of the suprachiasmatic nucleus regulatory output pathway. Furthermore, we observed that acute withdrawal from methadone markedly extended the period of high night AA-NAT activity in the pineal gland. This suggests that withdrawal from methadone, a widely used drug for the treatment of opioid dependence, may have stronger impact on melatonin synthesis than withdrawal from morphine.

P097: Evaluation of an oral morphine protocol for treatment of acute pain crisis in sickle cell patients in the outpatient setting

Introduction: Sickle cell vaso-occlusive crisis (VOC) is one of the most frequent causes of emergency visit and admission in children with this condition. With this study, we aim to evaluate whether the implementation of an oral morphine protocol has led to improved care of sickle cell disease (SCD), translated by a reduced hospitalization rate, an increased oral administration rate and faster opiate administration time, comparing cohorts of patients presenting to the emergency department (ED) and hematology outpatient clinic (HOC) with VOC pre and post implementation. Methods: Retrospective chart review of patients with SCD followed at CHU Ste-Justine, who presented to the ED and HOC with VOC, in the year pre and post implementation of the protocol. Patients with a VOC diagnosis during the study periods were selected in each department’s database. The primary outcome was to evaluate the hospitalization rate. The rate of oral administration, as well as the opiate administration time from inscription in the ED or arrival in the HOC were also calculated. We estimated that 35 patients per arm would be sufficiently powered to detect at least a 30% rate reduction of admissions, with a power of 80% and a significance of 0.05. Results: Over the two periods, a total of 105 patients (49 pre and 56 post) were included from the ED and 62 patients (36 pre and 26 post) from the HOC. Both departments showed a reduction in hospitalization rate: a difference of 48% (95% CI 32, 61) in ED and 38% (95% CI 13, 57) in HOC. Both showed an increase in the rate of oral administration: a difference of 36% (95% CI 19, 50) in ED and 33% (95% CI 8, 53) in HOC. There was a non-significant difference of 10 min (95% CI -10, 25) in the opiate administration time in ED, as opposed to HOC where a significant difference of -45 min (95% CI -71, -6) was found, with both presenting median times over the recommended 60 minutes post implementation. Both settings showed an increase in the percentage of patients without IVs; a difference of 17% (95% CI 4, 30) in ED and 55% (95% CI 72, 31) in HOC. Conclusion: This study validates the use of our oral morphine protocol for the treatment of VOC, by showing a significant reduction in hospitalization rates. Although delays remain in our opiate administration time, our protocol decreased the number of painful IV procedures.