Pharmacokinetics, pharmacodynamics, safety, and tolerability of dopamine-receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting.

INTRODUCTION: Dopamine (D)2,3-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). AREAS COVERED: Eight D2,3-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects. EXPERT OPINION: Since the introduction of D2,3-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)3-RAs and neurokinin (NK)1-RAs have been developed. The classical D2,3-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D2,3-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT3-RA, dexamethasone and a NK1-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D2,3-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D2,3-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.

The Nrf1 transcription factor is induced by patulin and protects against patulin cytotoxicity.

Patulin is a mycotoxin produced by a variety of molds that is found in various food products. The adverse health effects associated with exposure to patulin has led to many investigations into the biological basis driving the toxicity of patulin. Nevertheless, the mechanisms through which mammalian cells resists patulin-mediated toxicity is poorly understood. Here, we show that loss of the Nrf1 transcription factor renders cells sensitive to the acute cytotoxic effects of patulin. Nrf1 deficiency leads to accumulation of ubiquitinated proteins and protein aggregates in response to patulin exposure. Nrf1 expression is induced by patulin, and activation of proteasome genes by patulin is Nrf1-dependent. These findings suggest the Nrf1 transcription factor plays a crucial role in modulating cellular stress response against patulin cytotoxicity.

Perioperative Acetaminophen and Dexmedetomidine Eliminate Post-Operative Opioid Requirement following Pediatric Tonsillectomy.

Administration of post-operative opioids following pediatric tonsillectomy can elicit respiratory events in this patient population that often arise as central and obstructive sleep apnea. The primary objective of this study was to determine whether a perioperative combination of dexmedetomidine and acetaminophen could eliminate post-operative (in recovery and at home) opioid requirements. Following IRB approval and a waiver for informed consent, the medical records of 681 patients who underwent tonsillectomy between 1 January 2013 and 31 December 2018 were evaluated. Between 1 January 2013 and 31 December 2015, all patients received a fentanyl-sevoflurane-based anesthetic, without acetaminophen or dexmedetomidine, and received opioids in recovery and for discharge home. On 1 January 2016, an institution-wide practice change replaced this protocol with a multimodal perioperative regimen of acetaminophen (intravenous or enteral) and dexmedetomidine and eliminated post-operative opioids. This is the first time that the effect of an acetaminophen and dexmedetomidine combination on the perioperative and home opioid requirement has been reported. Primarily, we compared the need for rescue opioids in the post-anesthesia care period and after discharge. The multi-modal protocol eliminated the need for post-tonsillectomy opioid administration. Dexmedetomidine in combination with acetaminophen eliminated the need for post-operative opioids in the recovery period.

Parturient With Barnes Syndrome (Thoracolaryngopelvic Dysplasia) Undergoing Cesarean Delivery of a Neonate With Barnes Syndrome: A Case Report.

This case describes a parturient with Barnes syndrome, a rare disorder characterized by subglottic stenosis, thoracic dystrophy, and small pelvic inlet, who underwent cesarean delivery of a neonate diagnosed with Barnes syndrome. Live simulation training was performed by multidisciplinary team to prepare for the spinal anesthetic, personnel flow between 2 operating rooms, and management of various airway scenarios for the newborn. After delivery, the neonate underwent laryngoscopy-bronchoscopy with successful intubation in the operating room because of labored breathing. Airway evaluation revealed subglottic stenosis, tracheomalacia/bronchomalacia. Collaboration among perinatologists, obstetric/pediatric anesthesiologists, pediatric head and neck surgeons, and neonatologists was integral to perioperative management of both the mother and child.

Adverse events associated with procedural sedation in pediatric patients in the emergency department.

PURPOSE: To determine the agents used by emergency medicine (EM) physicians in pediatric procedural sedation and the associated adverse events (AEs) and to provide recommendations for optimizing drug therapy in pediatric patients. METHODS: We conducted a prospective study at Stanford Hospital's pediatric emergency department (ED) from April 2007 to April 2008 to determine the medications most frequently used in pediatric procedural sedation as well as their effectiveness and AEs. Patients, 18 years old or younger, who required procedural sedation in the pediatric ED were eligible for the study. The data collected included medical record number, sex, age, height, weight, procedure type and length, physician, and agents used. For each agent, the dose, route, time from administration to onset of sedation, duration of sedation, AEs, and sedation score were recorded. Use of supplemental oxygen and interventions during procedural sedation were also recorded. RESULTS: We found that in a convenience sample of 196 children (202 procedures) receiving procedural sedation in a university-based ED, 8 different medications were used (ketamine, etomidate, fentanyl, hydromorphone, methohexital, midazolam, pentobarbital, and thiopental). Ketamine was the most frequently used medication (88%), regardless of the procedure. Only twice in the study was the medication that was initially used for procedural sedation changed completely. Fracture reduction was the most frequently performed procedure (41%), followed by laceration/suture repair (32%). There were no serious AEs reported. CONCLUSION: EM-trained physicians can safely perform pediatric procedural sedation in the ED. In the pediatric ED, the most common procedure requiring conscious sedation is fracture reduction, with ketamine as the preferred agent.

Comparison of early and late extubation following single-stage anterior laryngotracheoplasty.

OBJECTIVE: To compare the outcomes of early versus late extubation after primary single-stage anterior laryngotracheoplasty (LTP) using thyroid ala graft performed at our tertiary care academic children's hospital. METHODS: Twenty-five pediatric patients underwent single-stage anterior LTP using thyroid ala grafts between September 2002 and June 2009. Initial trials of extubation were attempted in 15 patients on or prior to postoperative day (POD) 2 and in 10 patients on or after POD 3. The main outcome measures analyzed in this retrospective comparison study were complication rate, length of hospitalization, reintubation during hospitalization, need for additional airway procedures, and overall decannulation rate. RESULTS: The rates of various complications in each group were not statistically significant, with the exception of methadone taper. No patients in the early extubation group and four patients in the late extubation group required methadone taper [p<0.05]. The average length of hospitalization after extubation for the early extubation group was 16.5 days [SD=14.0] and 14.6 days [SD=7.7] for the late extubation group [p>0.05]. Six patients (40%) in the early extubation group and two (20%) in the late extubation group needed reintubation at some point during hospitalization post-LTP [p>0.05]. Ten patients [66.7%] in the early extubation group and eight [80%] in the late extubation group required additional airway procedures post-LTP [p>0.05]. Ultimately, 12 (80%) of the early extubation group and nine (90%) of the late extubation group were successfully decannulated at the time of most recent follow-up [p>0.05]. CONCLUSIONS: The differences in length of hospitalization, need for additional procedures, reintubation during hospitalization and overall decannulation rate between the early and late extubation groups after single-stage anterior LTP with thyroid ala graft were not statistically significant. Methadone taper was the only complication that was statistically significantly higher in the late extubation group.

Pediatric primary anterior laryngotracheoplasty: Thyroid ala vs costal cartilage grafts.

OBJECTIVE: To compare outcomes with the use of thyroid ala cartilage (TAC) and costal cartilage (CC) grafts in pediatric primary anterior laryngotracheoplasty (LTP). DESIGN: Retrospective comparison study. SETTING: Tertiary, academic children's hospital. PATIENTS: Of 45 laryngotracheal operations performed between June 2001 and October 2008 for laryngotracheal stenosis, 29 were primary anterior LTPs. The procedures used either TAC (n = 24) or CC (n = 5) grafts and were planned as either single-stage (TAC group, 22 patients; CC group, 2 patients) or multistage (TAC group, 2 patients; CC group, 3 patients). MAIN OUTCOME MEASURES: Operative time, length of intubation, graft-specific complications, need for additional airway procedures, and overall decannulation rate. RESULTS: The mean (SD) operative times were 222 (56) minutes for TAC grafts and 363 (59) minutes for CC grafts (P = .005). For single-stage LTPs that were decannulated, the mean (range) length of intubation was 3.3 (1-11) days for TAC grafts (n = 18) and 3 (1-5) days for CC grafts (n = 2) (P = .90). Graft-specific complications occurred in 17% of TAC grafts (n = 4) and 20% of CC grafts (n = 1) (alpha > 0.05). Symptomatic stenosis requiring additional surgical intervention occurred in 43% of TAC grafts (n = 10) and 60% of CC grafts (n = 3) (alpha > 0.05). Patients underwent decannulation in 83% of TAC grafts (n = 19) and 80% of CC grafts (n = 4) (alpha > 0.05). CONCLUSIONS: In primary anterior LTPs, TAC grafts require significantly less operative time than CC grafts (P = .005). There were no statistically significant differences in length of intubation, frequency of graft-specific complications, or decannulation rates between TAC and CC grafts in primary anterior LTPs.

Comparison of intraoperative bleeding between microdebrider intracapsular tonsillectomy and electrocautery tonsillectomy.

OBJECTIVES: We sought to assess the quantity of intraoperative bleeding from microdebrider intracapsular tonsillectomy (IT) relative to electrocautery tonsillectomy (ET). METHODS: Intraoperative tonsil bleeding was measured prospectively for all children younger than 19 years of age who underwent primary tonsillectomy for recurrent tonsillitis or adenotonsillar hypertrophy at a tertiary care academic children's hospital. We performed IT in 57 patients (33 male, 24 female; mean age, 64.3 months) and ET in 51 patients (20 male, 31 female; mean age, 92.4 months). RESULTS: Microdebrider IT resulted in more intraoperative bleeding than ET (27.9 versus 8.7 mL, p = 0.003; and 1.2 versus 0.2 mL/kg, p <0.001). The median and maximum blood losses, respectively, were 0.6 and 9.5 mL/kg for IT and 0 and 2.0 mL/kg for ET. Blood loss for ET was not related to whether a resident versus an attending physician was the operating surgeon (p = 0.11). A linear regression model did not demonstrate greater bleeding with recurrent tonsillitis (IT, p = 0.39; ET, p = 0.89) or with increased patient age (IT, p = 0.08; ET, p = 0.62). CONCLUSIONS: Microdebrider IT produces more intraoperative bleeding than ET. The difference in blood loss is statistically but not clinically significant. Microdebrider IT causes bleeding within acceptable limits, and thus patients and physicians should not be discouraged from choosing this procedure solely on the basis of the amount of intraoperative blood loss.

Hepatitis vaccination and prophylaxis.

The three most commonly identified causes of viral hepatitis in the United States are hepatitis A virus (HAV), hepatitis B virus (HBV), and hepatitis C virus (HCV). Hundreds of millions of people worldwide are infected by these viruses; many experience illness as a result. This article discusses current recommendations for vaccination and other forms of prophylaxis aimed at minimizing the clinical effects of these viruses.

Using risk management files to identify and address causative factors associated with adverse events in pediatrics.

We report a retrospective analysis of 84 consecutive pediatrics-related internal review files opened by a medical center's risk managers between 1996 and 2001. The aims were to identify common causative factors associated with adverse events/adverse outcomes (AEs) in a Pediatrics Department, then suggest ways to improve care. The main outcome was identification of any patterns of factors that contributed to AEs so that interventions could be designed to address them. Cases were noted to have at least one apparent contributing problem; the most common were with communication (44% of cases), diagnosis and treatment (37%), medication errors (20%), and IV/Central line issues (17%). 45% of files involved a child with an underlying diagnosis putting her/him at high risk for an adverse outcome. All Pediatrics Departments face multiple challenges in assuring consistent quality care. The extent to which the data generalize to other institutions is unknown. However, the data suggest that systematic analysis of aggregated claims files may help identify and drive opportunities for improvement in care.

Radiography cannot examine disc injuries secondary to burst fracture: quantitative discomanometry validation.

STUDY DESIGN: An in vitro biomechanical study. OBJECTIVE: To examine disc integrity at levels adjacent and next adjacent to the fractured vertebra and to determine if the disc injury can be revealed by radiographs. SUMMARY OF BACKGROUND DATA: Thoracolumbar burst fracture is one of the most common spinal injuries. A fractured vertebra is easy to recognize, but the associated disc injuries are less well known. The disc injury may not be apparent in radiographic images. Quantitative discomanometry, which measures disc pressure and the injected volume, has been found to detect disc injury. METHODS: Nine specimens (T11-L3) with L1 burst fracture included adjacent discs (T12-L1 and L1-L2) and next-adjacent discs (T11-T12 and L2-L3) and were examined with radiographs and quantitative discomanometry, before and after the burst fracture. Statistical analyses were used to determine if the nine quantitative discomanometry parameters, in each of the four discs, were changed by the burst fracture and if the two next adjacent discs sustained different injuries. RESULTS: After the burst fracture both the adjacent discs were shown to be injured by both radiographic and quantitative discomanometry examinations. Whereas both next-adjacent discs were found to be uninjured by radiograph examination, the quantitative discomanometry found the lower next-adjacent disc (L2-L3) to be injured. CONCLUSIONS: Quantitative discomanometry was successful in finding disc injury, where the radiographs found none. The lower level, next adjacent disc is susceptible to injury during the burst trauma.