Use Of Antiemetics Research Articles

Assessing risk perception of anti-emetic drug use during pregnancy and the potential impact of risk communication tools: A study protocol

Assessing risk perception of anti-emetic drug use during pregnancy and the potential impact of risk communication tools: A study protocol

Exploring sleep disturbance among adults with primary or secondary malignant brain tumors and their caregivers.

Emerging evidence supports the clinical impact of sleep disturbance (SD) on cancer patients. This study aimed to determine the prevalence and predictors of SD in people with malignant brain tumors and caregivers, and explore any relationship between the patient-caregiver dyad's sleep. Eighty-one adults with primary malignant (91%) or metastatic (9%) brain tumors and their family caregivers (n = 44) completed a series of self-report questionnaires, including the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index, and the drowsiness item of The MD Anderson Symptom Inventory-Brain Tumor in an Australian ambulatory neuro-oncology setting. Participants were grouped by the PSQI cutoff (SD > 5), and binary logistic regression analyses were performed to identify risk factors. Of patients, 53% reported SD and 15% of those clinically significant insomnia, and 27% reported moderate to severe daytime drowsiness. Whereas anxiety, depression, fatigue, pain, neurocognitive symptoms, and antiemetic use were higher in patients with SD, fatigue and KPS were strong predictors of SD. In caregivers, 55% reported poor sleep and 13% clinical insomnia. Anxiety, caregiver burden, and comorbid illness were significantly associated with caregivers' SD. The individual's SD did not affect the chance of the other member of the patient-caregiver dyad experiencing SD. More than half the sample had sleep disturbance, which was linked to many concomitant symptoms, such as fatigue in patients and anxiety in caregivers, potentially contributing to distress and functional impairment. Understanding underlying mechanisms of SD, the potential use of these clinical predictors in care settings, and options for management is warranted.

Surgeon-Placed Continuous Wound Infusion Pain Catheters Markedly Decrease Narcotic Use and Improve Outcomes After Pancreatic Tumor Resection.

Pancreatectomy results in significant postoperative pain and typically requires opioid analgesia for adequate pain control. Local anesthetics may decrease postoperative pain and opioid requirements but can be limited by onset of action, duration of effect, and inability to titrate dosing after administration. This can be overcome by surgeon placement of tunneled peri-incisional catheters with continuous wound infusion (CWI). This retrospective cohort study analyzed patients undergoing open pancreatic tumor resection. All the patients received patient-controlled analgesia (PCA), enabling an objective comparison of opioid requirements, and underwent the same recovery pathway. The patients received CWI (n = 45), PCA alone (n = 11), or epidural analgesia (EA) (n = 9). The primary outcome was total opioid use in terms of intravenous morphine milligram equivalents (MMEs) and patient-reported pain scores on a numeric rating scale (NRS) of 0 to 10. No differences in baseline patient or tumor characteristics were observed. In both the uni- and multivariate analyses, CWI was associated with lower opioid use than PCA (MME, 83 vs 207mg; p = 0.004) or EA (MME, 83 vs 156mg; p < 0.001) without having a negative impact on pain scores. Furthermore, CWI was associated with a greater percentage of time that patients experienced optimal pain control (NRS, ≤ 4: 63% vs 50%; p = 0.033) and a shorter time to PCA independence (4.0 vs 4.9days; p = 0.004) than PCA alone. In addition, CWI was associated with earlier ambulation [EA vs CWI: odds ratio (OR), 0.05; p = 0.021], improved spirometry performance (CWI vs PCA: regression coefficient (coef), 267; p = 0.013), and earlier urinary catheter removal (EA vs CWI: coef, 1.30; p = 0.013). The findings showed no differences in time to return of bowel function, antiemetic use, or hospital length of stay. After open pancreatic tumor resection, CWI is safe and associated with decreased opioid requirements and improved functional outcomes without a negative impact on pain scores, supporting its potential for preferred use over PCA or EA alone.

124. Enhanced recovery after surgery protocols in spine surgery: harnessing national data to identify optimal protocols

BACKGROUND CONTEXT Enhanced recovery after surgery (ERAS) protocols are increasingly used in spine surgery and various studies have demonstrated benefits. However, protocols consist of separate components which are variably used leading to significant discrepancies in applications. Data is currently lacking on which combinations are the most commonly used and the most effective. PURPOSE To understand what combinations of ERAS components are being implemented for patients undergoing posterior lumbar fusion surgery and which are the most effective in improving outcomes in a general population using national claims data. STUDY DESIGN/SETTING Data were extracted from the Premier Healthcare claims database (2006-2016). We identified 7 ERAS components commonly included in spine ERAS protocols: (1) use of multimodal analgesia, (2) use of tranexamic acid (TXA), (3) use of antiemetics on the day of surgery, (4) early physical therapy -on the day of surgery or the day after-, (5) avoidance of a urinary catheter, (6) avoidance of patient-controlled analgesia (PCA), and (7) avoidance of wound drains. PATIENT SAMPLE This retrospective cohort study included 132,802 posterior lumbar fusion surgeries. OUTCOME MEASURES The main outcomes were length of stay, any complication (cardiopulmonary, renal, and wound complications, stroke, sepsis, thromboembolism, delirium, and inpatient falls), and cost of hospitalization. METHODS Mixed-effects models measured associations between the most common ERAS combinations and outcomes. The most commonly occurring ERAS combinations (those that represent ≥50% or more of cases) were assessed separately for the 2006-2012 and 2013-2016 time periods, given the increasing use of ERAS protocols over time. Odds ratios (OR) and 95% confidence intervals (CI) are reported. RESULTS Overall, 74% (n=97,793) of procedures were in 2006-2012 while 26% (n=35,009) were in 2013-2016. In the 2006-2012 period, the most common ERAS combination was the use of six ERAS components: use of multimodal analgesia, antiemetics, early physical therapy, avoidance of a urinary catheter, PCA and drains (10%, n=9,425). The same combination was most commonly seen in the 2013-2016 period (19%, n=6,646). TXA was not among the most commonly used combinations. After adjustment for relevant covariates, the most pronounced beneficial effects in the 2006-2012 period were seen for combinations 2 (no multimodal analgesia) and 5 (no multimodal analgesia and no avoidance of a PCA) for the outcome of “any complication”: OR 0.73 CI 0.67-0.80 and OR 0.73 CI 0.65-0.82, respectively; both p CONCLUSIONS In this large observational study using data on patients undergoing posterior lumbar fusion surgery we were able to discern substantial variations in ERAS component combinations, which decreased in more recent years. Interestingly, while different ERAS combinations were identified in each time period, the maximum benefit in terms of complication reduction was more pronounced in the 2006-2012 period with an overall lower use of ERAS protocols. Moreover, TXA was not seen among the most commonly used ERAS protocol combinations, indicating potential room for improvement. These findings may inform future clinical trials comparing various ERAS protocols. FDA DEVICE/DRUG STATUS This abstract does not discuss or include any applicable devices or drugs.

Evaluation of inpatient postpartum recovery using the Obstetric Quality of Recovery-10 patient-reported outcome measure: a single-center observational study

Few adequately validated patient-reported outcome measures are available, which can assess recovery profiles following childbirth. We aimed to determine whether quantitative recovery (using the Obstetric Quality of Recovery-10 patient-reported outcome measure) was superior following vaginal delivery compared with cesarean delivery and evaluate validity, reliability, and responsiveness of this patient-reported outcome measure in the obstetrical setting in the United States. Women recruited into this single-center observational cohort study completed the Obstetric Quality of Recovery-10 and EuroQol 5-dimension 3L patient-reported outcome measures within 72 hours of childbirth. We assessed the validity with hypothesis testing and structural validity. In hypothesis testing, the primary outcome was Obstetric Quality of Recovery-10 scores after vaginal vs cesarean delivery. Secondary outcomes were differences in Obstetric Quality of Recovery-10 scores for vaginal delivery following induction of labor vs spontaneous labor and scheduled vs unplanned cesarean delivery, correlation with clinical parameters (American Society of Anesthesiologists classification grade, body mass index, length of hospital stay, estimated blood loss, transfusion requirement, antiemetic use, and neonatal intensive care unit admission), and qualitative ranking of Obstetric Quality of Recovery-10 items for each delivery mode. Structural validity was assessed by determining the correlation of the Obstetric Quality of Recovery-10 scores with the EuroQol 5-dimension 3L and global health visual analog scale scores. Reliability was assessed using Cronbach alpha and inter-item correlation of Obstetric Quality of Recovery-10 items. Responsiveness was assessed by evaluating the change in Obstetric Quality of Recovery-10 scores over the 72-hour postpartum period. Data from 215 women were analyzed. In hypothesis testing, the median (interquartile range) Obstetric Quality of Recovery-10 scores were higher following vaginal delivery than cesarean delivery (86 [77-94] vs 77 [64-86], respectively; P<.001). Multivariate model demonstrated that Obstetric Quality of Recovery-10 scores were significantly lower after cesarean delivery when adjusting for American Society of Anesthesiologists classification grade, age, body mass index, and ethnicity (R=-8.97; P<.001). Obstetric Quality of Recovery-10 scores were similar between induction of labor and spontaneous labor, and scheduled cesarean delivery and unplanned cesarean delivery. Obstetric Quality of Recovery-10 was correlated with length of hospital stay (R=-0.248; P<.001), estimated blood loss (R=-0.3429; P<.001), transfusion requirement (R=-0.140; P=.041), and antiemetic use (R=-0.280; P<.001). The highest ranked Obstetric Quality of Recovery-10 items were ability to hold baby, feeling in control, and ability to look after personal hygiene. The lowest ranked items were pain and shivering. In structural validity, correlation of Obstetric Quality of Recovery-10 score was moderate with the global health visual analog scale (r=0.511) and EuroQol 5-dimension 3L scores (r=-0.509). In reliability, Cronbach alpha was 0.72 and more than 80% of individual items correlated. In responsiveness, Obstetric Quality of Recovery-10 scores did not change significantly over the study period. Quantitative inpatient recovery following vaginal delivery is superior to cesarean delivery. The Obstetric Quality of Recovery-10 appears to be a valid and reliable patient-reported outcome measure following these delivery modes. Further studies are needed to determine how to improve recovery domains identified in this study, to evaluate Obstetric Quality of Recovery-10 in different languages and determine whether these domains impact outcomes beyond hospitalization.

Antidopaminergic antiemetics and trauma-related hospitalization: A population-based self-controlled case series study.

The aim of this study was to evaluate the risk of trauma associated with the use of antidopaminergic antiemetics in a real-world setting. A self-controlled case series analysis was performed using the EGB database, the representative sample of the French national healthcare insurance system database. All subjects aged 18 years and over who presented with at least 1 trauma-related hospitalization and 1 supply for domperidone, metoclopramide or metopimazine between 2009 and 2014 were included in the study. Associations were evaluated by incidence rate ratios. Included exposed cases were 7610 for domperidone cohort, 2189 for metoclopramide and 3911 for metopimazine. Incidence rate ratio for trauma-related hospitalization during the first 7 days of exposure period compared to unexposed period was 1.53 (95% confidence interval 1.29-1.80) for domperidone, 2.00 (1.37-2.91) for metoclopramide and 2.30 (1.71-3.09) for metopimazine. We found an increased risk of hospitalizations for traumatic injuries for the main marketed antidopaminergic antiemetics during the first days of use. The highest risk was observed for metopimazine, which could relate to its pharmacological profile and central effects.

Effects of Peppermint Aromatherapy on Postoperative Nausea and Vomiting

PurposeStandardized order sets for postoperative patients often include antiemetic medications only for postoperative nausea and vomiting (PONV). The purpose of this study was to compare the incidence of PONV in patients receiving peppermint aromatherapy and usual care to patients receiving only usual care. DesignQuasi-experimental research design used to evaluate the ability of peppermint aromatherapy to decrease PONV and antiemetic use postoperatively. MethodsIntervention group received peppermint aromatherapy with a control group receiving standard of care. The nausea scale with descriptors was used to evaluate PONV. FindingsDescriptive statistics and a χ2 test revealed no statistical significance (P = .28). However, peppermint aromatherapy was preferred by many patients as indicated by patients' statements and decreased ratings and complaints of nausea. ConclusionsThe peppermint aromatherapy was favorably received by many of the postoperative patients and may be an effective adjunct treatment with antiemetics for PONV.

Opioid-free anesthesia for patients undergoing mastectomy: A matched comparison.

Opioid-free anesthesia (OFA) is being implemented in breast surgery due to increased awareness of adverse effects and the national opioid crisis. The objective of this study was to examine the effect of OFA on postoperative pain and postoperative nausea and vomiting (PONV) in mastectomy patients. A single-institution matched-cohort study was conducted from 2014 to 2017 on 48 women undergoing mastectomy, with the majority also undergoing immediate prosthetic-based reconstruction. Patients received either conventional anesthesia (CA) or a novel OFA regimen. Primary outcomes included postoperative pain scores, opioid use, and need for antiemetics that were evaluated both in the PACU and on the hospital floors. No significant differences were found in PACU opioid or antiemetic use between OFA and CA. Pain scores in PACU and on POD0 were not significantly different. There was a significant but modest decrease on POD1 in OFA patients (3.9 vs. 5.1, P=.046). Additionally, patients with higher intraoperative opioid regimens experienced significantly increased PONV (P=.023). This study demonstrated the efficacy of OFA in controlling postoperative pain and nausea compared to a traditional opioid-based regimen. Regardless of intraoperative opioids, patients experienced similar postoperative opioid requirements and PONV with decreased pain scores. Thus, OFA is feasible in mastectomy patients and should be further evaluated in select patients.

Post-operative Nausea and Analgesia Following Total Mastectomy is Improved After Implementation of an Enhanced Recovery Protocol.

Enhanced Recovery Protocols (ERPs) provide a multimodal approach to perioperative care, with the aims of improving patient outcomes while decreasing perioperative antiemetic and narcotic requirements. With high rates of post-operative nausea or vomiting (PONV) following total mastectomy (TM), we hypothesized that our institutional designed ERP would reduce PONV while improving pain control and decrease opioid use. An ERP was implemented at a single institution for patients undergoing TM with or without implant-based reconstruction. Patients from the first two months of implementation (ERP group, N = 72) were compared with a retrospective usual-care cohort from a three-month period before implementation (UC group, N = 83). Outcomes included PONV incidence, measured with antiemetic use; patient-reported pain scores; perioperative opioid consumption, measured by oral morphine equivalents (OME); and length of stay (LOS). The characteristics of the two groups were similar. PONV incidence and perioperative opioid consumption were lower in the ERP than the UC group (21% vs. 40%, p 0.011 and mean 44.1 OME vs. 104.3 OME, p < 0.001), respectively. These differences in opioid consumption were observed in the operating room and post-anesthesia care unit (PACU); opioid consumption on the floor was similar between the two groups. Patient-reported pain scores were lower in the ERP than the UC group (mean highest pain score 6.4 vs. 7.4, p 0.003). PACU and hospital LOS were similar between the two groups. ERP implementation was successful in decreasing PONV following TM with and without reconstruction, while simultaneously decreasing overall opioid consumption without compromising patient comfort.

Drug treatment of acute vertigo

Acute vertigo is a severe condition that requires urgent treatment. Vertigo can be caused by peripheral or central vestibular disorders of various etiopathology. Whatever the reason of vestibular dizziness, it is characterized by severe attacks with imbalance, nausea and vomiting in the acute period. Symptomatic treatment consists of vestibular suppressants and antiemetic drugs. There are several key principles regarding management of patients with vertigo that includes combined use of vestibular suppressants and antiemetics, which allows potentiation of their effects, limitation the use of symptomatic therapy to 2–3 days and perhaps earlier initiation of vestibular rehabilitation which effectiveness can be improved with agents that stimulate central vestibular adaptation.

Droperidol Reduces Postoperative Nausea and Vomiting and Supports the Continuation of Intravenous Patient-Controlled Analgesia with Fentanyl.

To examine the impact of adding droperidol to fentanyl-based intravenous patient- controlled analgesia (IVPCA) on the discontinuation of IVPCA use due to postoperative nausea and vomiting (PONV). Patients who underwent surgeries other than abdominal surgeries and used IVPCA between April 2014 and March 2018 were selected. Patients using IVPCA with fentanyl alone were compared to patients using droperidol added to IVPCA. Patients were allocated to one of two groups depending on the drug used for IVPCA: 1) control group, fentanyl alone; 2) droperidol group, droperidol with fentanyl. The primary endpoint was the discontinuation of IVPCA due to PONV. Secondary endpoints included PONV within 48 hours after surgery, the number of antiemetics used, pain score, and adverse effects. Propensity score matching was used to control the differences in clinical features among patients. Among the 793 patients initially enrolled in this study, 145 were excluded via propensity score matching; 364 of the remaining patients received IVPCA supplemented with droperidol. Propensity score matching showed that discontinuation of IVPCA due to PONV was significantly decreased in the droperidol group compared to the control group (P = 0.01). Further, compared with the control group, the droperidol group had reduced nausea up to 24 hours after surgery (P < 0.01), and the number of vomiting episodes and use of antiemetics decreased within 12 hours after surgery (P < 0.01). The addition of droperidol to IVPCA is associated with a decrease in PONV, as well as the improved continuation of pain treatment with fentanyl-based IVPCA, similar to IVPCA with morphine. However, it is necessary to monitor the side effects of this treatment.

Repeat Doses of Dexamethasone up to 48 Hours Further Reduce Pain and Inflammation After Total Hip Arthroplasty: A Randomized Controlled Trial

BackgroundThe optimal dose regimen of dexamethasone in total hip arthroplasty (THA) is unclear. This study was conducted to compare the effects among 1-dose, 2-dose, and 3-dose dexamethasone in THA. MethodsOne hundred fifty patients were randomized to receive a single preoperative dose of 10-mg dexamethasone (group A, 50 patients), or another dose of 10-mg dexamethasone 24 hours later (group B, 50 patients), or another 2 doses of 10-mg dexamethasone 24 and 48 hours later (group C, 50 patients). The primary outcome was postoperative pain level. The use of analgesic and antiemetic rescue; incidence of postoperative nausea and vomiting; C-reactive protein and interleukin-6 levels; range of motion; and complications were also compared. ResultsThe dynamic pain scores were lower for groups B and C compared to group A on postoperative days 2 and 3. Such difference was also detected between groups B and C on postoperative day 3. C-reactive protein and interleukin-6 levels were lower in groups B and C than in group A at 48 and 72 hours postoperatively. Such difference was also observed between groups B and C at 72 hours postoperatively. Patients in groups B and C had reduced rescue analgesic use, and improved range of motion compared to patients in group A. There were no differences among 3 groups regarding the rescue antiemetic use, postoperative nausea and vomiting occurrence, and complications. ConclusionAdditional administrations of dexamethasone after THA could provide sustained pain relief and inflammatory control. Besides, the 3-dose regimen was more effective than the 2-dose regimen in terms of the analgesic and anti-inflammatory effects. Level of EvidenceI

Pain during medical abortion in early pregnancy in teenage and adult women.

Women experience pain during medical abortion, yet optimal pain management remains unclear. We studied the pain experience and need of analgesics during early medical abortion (≤63days of gestation) among teenage and adult women. We also assessed predictive factors of severe pain. We recruited 140 primigravid women: 60 teenagers and 80 adult women aged between 25 and 35years old. The group of teenagers included 19 women under the age of 18years old (minors). The abortion was performed with mifepristone (200mg) followed by vaginal misoprostol (800μg), mainly self-administered at home for adults. Minors were hospitalized during misoprostol administration. Pain medication consisted of ibuprofen 600mg and paracetamol 1000mg, first doses taken simultaneously with misoprostol and repeated, if needed, up to three times daily. Additional opiates (mainly tramadol or oxycodone) were administered at hospital if needed. Pain was measured using the visual analogue scale (VAS, 0-100mm). The maximal pain VAS (median, interquartile range) was 75 (54-91). Of all the women, 57.7% experienced severe pain (VAS ≥70) during abortion care and 93.5% of women needed additional analgesics in addition to prophylactic pain medication. Teenagers needed additional analgesics more often than adults (5 [3-8] vs 3 [2-6] times, P=.021); 38.0% of all teenagers (64.7% of the minors) received additional opiates compared with 7.9% in adult women. Severe pain (VAS ≥70) was associated with history of dysmenorrhea (adjusted odds ratio [OR] 2.60 [95% confidence interval [CI] 1.21-5.59, P=.014]), anxiety at baseline (2.64 [1.03-6.77], P=.044) and emesis during abortion (5.24 [2.38-11.57], P<.001). Hospital administration of misoprostol did not lower the risk for severe pain experience (OR 0.84 [95% CI 0.34-2.05], P=.694). Satisfaction with care was high in study population (median VAS 91 [interquartile range 79-97]) and was not associated with the use of narcotic analgesic or place of misoprostol administration. Pain intensity was high both in teenage and adult women undergoing medical abortion, yet satisfaction on care was high. More effective analgesics than ibuprofen and paracetamol should be offered to all women undergoing early medical abortion, especially to those with history of dysmenorrhea. Also, routine use of antiemetics might be advisable.

Tu1165 CHARACTERIZATION AND FINANCIAL BURDEN OF PATIENTS WITH INADEQUATE AND INCOMPLETE BOWEL PREP AT AN ACADEMIC TERTIARY CENTER-- A PILOT STUDY

Bowel prep is inadequate in one third of all inpatient colonoscopies even after educational interventions and regimen variations. Incomplete intake of bowel prep by inpatients may go unrecognized by the gastroenterologist until the procedure date, creating unnecessary delays and extending hospital admission and/or requiring repeat colonoscopy. Focusing on nausea, prep quantity consumed and need for delay, we aimed to identify modifiable risk factors for inadequate bowel prep, and estimated the burden to the healthcare system of suboptimal inpatient bowel prep. We prospectively collected data for all inpatient colonoscopies in a tertiary center from July-November 2019. We excluded patients who prepped via feeding tube or with planned extended prep, and emergent colonoscopies. We collected demographics, amount of prep consumed, prep duration, nausea, antiemetic use, delays due to incomplete prep, and prep quality. We grouped patients by adequacy of prep, time to prep completion, and nausea. Avoidable charge estimates, obtained from www.healthcarebluebook.com and the hospital billing department, were calculated based on need for repeat colonoscopy (including technical and professional charges for colonoscopy with anesthesia) and avoidable admission days. We identified 74 colonoscopies that met inclusion criteria: 71 used polyethylene glycol (PEG) with electrolytes, and 3 PEG. 2 were canceled for prep intolerance. 16 (22%) patients had inadequate bowel prep. These patients accounted for nearly all incurred avoidable healthcare charges (Table 1). 9 (12%) patients required delay of ≥1 day for additional prep, totaling 12 extra admission days. 12 (17%) needed an extra half day. These 21 patients (Delay) had more nausea, lower prep quality and more inadequate prep (RR=4.05) despite consuming more prep, and incurred considerably more avoidable healthcare charges ($68,350 vs. $28,050) even while excluding the 12 half-day delays (Table 2). 12(17%) patients had nausea, 7 received antiemetics. These had high risk of delay (RR=2.5), trended to increased risk of inadequate prep, and incurred avoidable charges at a higher rate (Table 2). Antiemetic use did not improve outcomes. In a tertiary center, nearly one quarter of inpatients have inadequate bowel prep and 30% require cancellation or delay due to incomplete prep at scheduled procedure time. Over a 5-month period this created an estimated $96,400 of avoidable healthcare charges. Need for delay is an important risk factor for inadequate prep. Nausea is a risk factor for procedure delay and possibly for inadequate prep too. These are potentially modifiable risk factors. While this study does not show efficacy of antiemetics or delays for additional prep, further study of proactive and preemptive management of patients at risk for delay and inadequate prep is warranted.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A phase Ib study of oral Chk1 inhibitor LY2880070 as monotherapy in patients with advanced or metastatic cancer.

3579 Background: LY2880070 (LY) is an orally-administered, selective adenosine triphosphate-competitive inhibitor of checkpoint kinase 1 (Chk1). LY blocks the checkpoint response, and Chk1 inhibition results in mitotic catastrophe to produce apoptosis. Methods: This 2-part, open-label multi-center study explores the safety, pharmacokinetics (PK) and anti-tumor activity of LY in patients with advanced or metastatic cancers. The primary objective of this study was to determine the maximum tolerated dose (MTD) for multiple escalating oral doses of LY. Secondary objectives were to: 1) Characterize the dose-limiting toxicities (DLTs) and overall safety profile for LY; 2) Evaluate the PK of LY; and 3) Evaluate the anti-tumor activity of LY. Patients received LY orally in 21-day cycles in two treatment arms: 1) A multiple ascending dose (MAD) arm in patients with normal/intermediate CYP2D6 metabolism; or 2) An arm with LY administered as monotherapy to CYP2D6 poor metabolizers. Results: The MTD in normal/intermediate CYP2D6 metabolizers was 200 mg BID daily. A dose of 400 mg QD was not tolerated even with the use of anti-emetics. However, BID administration (same total daily dose) made LY tolerable. Dose-limiting toxicities were predominantly vomiting, nausea, and fatigue, and appeared to be correlated with Cmax. The mean half-life was 5.35 (+/- 2.3) hours. BID dosing provided maintenance of the AUC (3271.4 h∙ng/mL 200 mg BID vs 3377.9 h∙ng/mL 400 mg QD) while lowering Cmax (350.0 ng/mL 200 mg BID vs 691.9 ng/mL 400 mg QD) and increasing Cmin, compared to QD dosing of the same total daily dose. Importantly, BID administration of 200 mg LY resulted in a median Cmin at steady-state that remains above the IC80 for 12 h/day and above the IC50 for 24 h/day. Five patients had a best response of SD for a duration of ≥ 6 cycles. Conclusions: LY was tolerated in a daily BID schedule. The toxicity profile can be modulated by changing the dosing frequency from QD to BID while administering the same daily dose. LY may be a potential combination therapy with DNA damaging agents. Study #: NCT02632448 . This study is sponsored by Esperas Pharma Inc., 1255 boul. Robert-Bourassa #1610, Montreal, Qc, H3B 3X3. Clinical trial information: NCT02632448 .

The use of olanzapine as an antiemetic in palliative medicine: a systematic review of the literature

BackgroundOlanzapine is an atypical antipsychotic that has affinity for many central nervous system receptors. Its efficacy is supported by several studies in the prevention and treatment of chemotherapy-induced nausea and vomiting. No recommendations exist on the antiemetic use of olanzapine in the palliative care setting. The aim of this work is to complete the initial work of Fonte et al. published in 2015, to determine whether the literature supports the use of olanzapine as an antiemetic in palliative situations and, in practice, to propose a therapeutic schema adapted to the palliative setting.MethodsSystematic review of the literature according to the PRISMA criteria. We searched the PubMed, Cochrane, RefDoc, EMBase databases and the gray literature databases. The bibliographic search was conducted between November 2016 and August 2017.ResultsThirteen articles were included: 2 case studies, 3 case series, 3 retrospective studies, 2 prospective studies, 2 literature reviews. All studies concluded on the efficacy of olanzapine as an antiemetic in the palliative care setting. No serious adverse effects were reported. Based on the data from the literature review, we propose a therapeutic scheme adapted to the palliative care context.ConclusionAction of olanzapine on many receptors and its tolerance profile make it an interesting antiemetic treatment in palliative medicine. But to date, studies are scarce and have a low statistical power. Further investigation is therefore needed to determine the benefit of this treatment in palliative care patients, compared to usual treatments.

Metoklopramid Kullanımı Sonrası Gelişen Malign Nöroleptik Sendrom: Olgu Sunumu

Malign nöroleptik sendrom (MNS), antipsikotik ilaçların nadir görülen bir yan etkisidir. Sendrom, rijidite, titreme, taşikardi, ateş yüksekliği, bilinç değişikliği, otonomik disfonksiyon, yüksek serum kreatinin fosfokinaz (CPK) ve lökositoz ile karakterize olan bir tablodur. Antipsikotik ilaç kullanan hastalarda MNS insidansı %0,02-3 arasında değişir. Etiyolojide antiemetiklerin kullanımı, elektrolit düzensizlikleri (özellikle hipopotasemi), organik beyin sendromu, malnütrisyon da rol oynayabilir. MNS, yaşamı tehdit eden bir durum olup, tanı ve tedavisinde zorluk olabilir. Bu olgu sunumunda, bilinen kronik hastalığı olmayan hastada gelişen tedavisi ve tanısında oldukça zorlandığımız bir malign nöroleptik sendrom olgusunun sunulması amaçlanmıştır.

Efficacy of amisulpride on postoperative nausea and vomiting: a systematic review and meta-analysis.

Postoperative nausea and vomiting (PONV) remains a significant clinical problem for surgical patients. Amisulpride is a well-studied D2/D3 antagonist that has the potential to be used for preventing and treating PONV. Our aim was to assess the efficacy and safety of amisulpride for prevention and treatment of PONV through a systematic review and meta-analysis. A systematic literature search was performed using MEDLINE, EMBASE, PUBMED, clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials from their inception to Feb 15th, 2019. The efficacy outcome was the incidence of complete response, defined as no emesis and no rescue antiemetic use in a 24-h period after study drug administration. The safety outcomes were the adverse effects associated with amisulpride. Five studies comprising 3243 patients met inclusion critieria. Compared with placebo, amisulpride showed a significantly improved incidence of complete response [relative risk (RR): 1.30; 95% confidence interval (CI): 1.20-1.41; P < 0.00001, I2= 0%] with firm evidence from the trial sequential analysis. Particularly, the amisulpride at 5mg dose indicated a significant benefit than placebo [relative risk (RR): 1.28; 95% confidence interval (CI): 1.18-1.39; P < 0.00001, I2= 4%]. The adverse event profile of amisulpride was generally similar to the placebo. Based on our findings, low-dose, intravenous amisulpride is safe and efficacious for the prevention and treatment of PONV compared to placebo. Further studies are needed to explore the optimal dose and timing. PROSPERO: CRD42019121483.

Pharmacogenetics of antiemetics for chemotherapy-induced nausea and vomiting: A systematic review and meta-analysis.

A substantial proportion of cancer patients experience chemotherapy-induced nausea and vomiting (CINV) despite the use of antiemetic drugs. Prevalent genetic polymorphisms involved in antiemetic drug metabolism, drug transport and receptor pathways likely affect the effectiveness of antiemetics. Knowledge on which polymorphisms to integrate into individualised clinical care is needed. We did a systematic review evaluating the association between polymorphisms and effectiveness of antiemetics in cancer patients receiving moderately to highly emetogenic chemotherapy. Twenty studies n = 2331 evaluated eight polymorphisms in five candidate genes involved in 5-HT3 antagonist pathways. HTR3C C1214G increased the risk of acute chemotherapy-induced vomiting in the dominant model (odds ratio (OR) = 2.67, 95 % confidence interval (CI): 1.08-6.63). ABCB1 C3435T reduced the risk of acute CINV in the recessive model (OR = 0.60, 95 % CI: 0.44-0.81). Future studies should evaluate candidate genes that affect pharmacogenetics of other antiemetics beside 5-HT3 antagonists.

Should Antiemetics be Given Prophylactically with Intravenous Opioids While Treating Acute Pain in the Emergency Department?: Clinical Practice Paper Approved by American Academy of Emergency Medicine Clinical Guidelines Committee.

It is common practice for emergency physicians to give parenteral opioids for acute pain, however, some treating physicians have concerns that using parenteral opioids can lead to nausea and vomiting when used alone. Therefore, antiemetics are often given prophylactically with opioids for nausea and vomiting in the emergency department (ED). This systematic review evaluates the use of prophylactic antiemetics with parenteral opioids for the treatment of acute pain in the ED. A 10-year literature search using keywords was performed in PubMed for English-language human studies. Abstracts were screened to identify high-quality studies, which then underwent a more rigorous structured review. The recommendations are made based on the literature review. Eight articles met criteria for structured review and citation in this article. These include one review article, two randomized controlled trials, three prospective observational trials, one retrospective study, and one pre- and post-intervention trial. Based on the literature review, routine use of prophylactic antiemetics are not indicated with administration of parenteral opioids for treatment of acute pain in the ED, as nausea and vomiting are infrequent side effects. The recent literature clearly demonstrates that there are potential undesirable side effects from the use of antiemetics when using opioids. However, one subgroup of patients, those with a known history of nausea and vomiting after opioid use or a history of travel sickness, may benefit from the use of prophylactic antiemetic when being treated with parenteral opioids.