Differential sensory block during labour epidural analgesia: a prospective observational study to investigate the relationship of lower and upper sensory block levels to cold, pinprick, and light touch.

PURPOSE: A zone of differential block to cold has been recently documented during labour epidural analgesia, with an upper sensory block level (USBL) and a lower sensory block level (LSBL). We aimed to determine the correlation between USBL and LSBL to cold and pinprick and sensory block level to light touch during labour epidural analgesia. METHODS: We conducted a prospective observational study in patients requesting labour epidural analgesia. We placed an epidural catheter at L2/L3 or L3/L4, followed by a programmed intermittent epidural bolus plus patient-controlled epidural analgesia regimen. We assessed the sensory block levels 140 min after administering the loading dose. The primary outcomes were the USBL and LSBL to cold and pinprick and the sensory block level to light touch. RESULTS: We studied 30 patients. The median [interquartile range (IQR)] USBL and LSBL to ice were T7 [T7-T6] and T9 [T10-T8], respectively. The median [IQR] USBL and LSBL to pinprick were T8 [T10-T6] and T10 [T12-T10], respectively. There was a strong correlation between USBL to ice and pinprick (Spearman correlation coefficient, 0.57) and between LSBL to ice and pinprick (Spearman correlation coefficient, 0.52). There was no significant correlation between sensory block level to light touch and either USBL or LSBL to ice or pinprick. CONCLUSION: We observed two sensory block levels to ice and pinprick. Further studies are required to understand if one modality-cold or pinprick-is superior to the other in assessing sensory block levels in this context. Light touch is unreliable as a modality of sensory block assessment during labour epidural analgesia. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05187962); registered 12 January 2022.

RéSUMé: OBJECTIF: Une zone de bloc différentiel de réaction au froid a récemment été documentée pendant l'analgésie péridurale obstétricale, avec un niveau de bloc sensoriel supérieur (USBL, pour upper sensory block level) et un niveau de bloc sensoriel inférieur (LSBL, pour lower sensory block level). Notre objectif était de déterminer la corrélation entre l'USBL et le LSBL au contact du froid et de la piqûre et le niveau de bloc sensoriel au toucher léger pendant l'analgésie péridurale obstétricale. MéTHODE: Nous avons mené une étude observationnelle prospective chez des patient·es demandant une analgésie péridurale obstétricale. Nous avons placé un cathéter péridural au niveau L2/L3 ou L3/L4, suivi d'une administration programmée de bolus périduraux plus un régime d'analgésie péridurale contrôlée par le/la patient·e. Nous avons évalué les niveaux de bloc sensoriel 140 min après l'administration de la dose de charge. Les critères d'évaluation principaux étaient l'USBL et le LSBL en réaction au froid et à la piqûre d'épingle et le niveau de bloc sensoriel en réaction au toucher léger. RéSULTATS: Nous avons étudié 30 patient·es. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la glace étaient situés au niveau T7 [T7-T6] et T9 [T10-T8], respectivement. Les USBL et LSBL médians [écart interquartile (ÉIQ)] à la piqûre étaient localisés au niveau T8 [T10­T6] et T10 [T12­T10], respectivement. Il y avait une forte corrélation entre l'USBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,57) et entre le LSBL à la glace et à la piqûre (coefficient de corrélation de Spearman, 0,52). Il n'y avait pas de corrélation significative entre le niveau de bloc sensoriel en réaction au toucher léger et l'USBL ou le LSBL en réaction à la glace ou à la piqûre. CONCLUSION: Nous avons observé deux niveaux de bloc sensoriel à la glace et à la piqûre. D'autres études sont nécessaires pour comprendre si une modalité ­ le froid ou la piqûre ­ est supérieure à l'autre pour évaluer les niveaux de bloc sensoriel dans ce contexte. Le toucher léger n'est pas fiable en tant que modalité d'évaluation du bloc sensoriel pendant l'analgésie péridurale obstétricale. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov (NCT05187962); enregistré le 12 janvier 2022.

Oxytocin at Elective Cesarean Delivery: A Dose-Finding Study in Pregnant People With Twin Pregnancy.

BACKGROUND: Multiple pregnancy is associated with higher risk of uterine atony, postpartum hemorrhage (PPH), blood transfusion, hysterectomy, and death. The optimal dose of oxytocin at cesarean delivery in people with twin pregnancy is unknown. We sought to determine the effective bolus dose of oxytocin required to initiate adequate uterine tone in 90% of people (ED90) with twin pregnancy undergoing elective cesarean delivery. Our hypothesis was that the dose of oxytocin would be higher than 0.5 international units (IU) but lower than 5 IU. METHODS: A double-blind dose-finding study using the biased coin up-down method was undertaken in people with twin pregnancy ≥36 weeks gestational age undergoing elective cesarean delivery under neuraxial anesthesia. Those with additional risk factors for PPH, apart from twin pregnancy, were excluded. Oxytocin was administered as an intravenous bolus over 1 minute on delivery of the second fetus. The first patient received 0.5 IU, and subsequent oxytocin doses were administered according to a sequential allocation scheme. The actual doses administered were 0.5, 1, 2, 3, 4, and 5 IU of oxytocin. The primary outcome was the response defined as the satisfactory uterine tone at 2 minutes after completion of administration of the oxytocin bolus, as assessed by the operating obstetrician. Secondary outcomes included need for rescue uterotonic drugs, adverse effects, and estimated blood loss. The ED90 was estimated using the Dixon-Mood and the isotonic regression methods. RESULTS: Thirty patients were included in study. The estimated ED90 of oxytocin was 4.38 IU (95% confidence interval [CI], 3.68-4.86 IU) and 3.41 IU (95% CI, 2.83-3.98 IU) by the isotonic regression and Dixon-Mood methods, respectively. Seven patients had inadequate tone at the 2-minute evaluation point and required rescue uterotonic drugs. The median (interquartile range [IQR]) estimated blood loss was 1031 mL (732-1462 mL) calculated by the change in 24-hour hematocrit. Incidence of hypotension after oxytocin administration was 27%, nausea 30%, and vomiting 17%. CONCLUSIONS: Our results demonstrated that people with twin pregnancy require a much higher dose of oxytocin than those with singleton pregnancies. We recommended people with twin pregnancies should receive an initial 5 IU bolus over at least 1 minute when undergoing elective cesarean delivery under neuraxial anesthesia.

Predictors and Hospital Outcomes in Pregnant Patients Undergoing Extracorporeal Membrane Oxygenation: A Nationwide Study.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with severe cardiorespiratory collapse. Although prior large database reviews of ECMO use in the peripartum population exist, they do not stratify by ECMO indication nor do they include obstetric conditions such as preeclampsia. Our objective was to characterize the incidence, indication-associated mortality, and factors associated with mortality in pregnant patients who underwent ECMO. METHODS: We examined the United States National Inpatient Sample database to identify hospitalizations for pregnancy from January 1, 2010 to December 31, 2016. We identified pregnant patients who underwent ECMO using International Classification of Diseases ninth and tenth revisions codes. The primary outcome was in-hospital all-cause mortality across pregnant patients who underwent ECMO for any indication. We evaluated the indication for ECMO, incidence, prevalence of risk factors, comorbidities and conditions, and their association with in-hospital mortality. RESULTS: Fifty-nine of 5'346,517 pregnant patients underwent ECMO during our study period (incidence, 1.1; 95% confidence interval [CI], 0.84-1.4 per 100,000 hospitalizations). Indications for ECMO support included respiratory failure (79.7%), cardiogenic shock (64.4%), or circulatory arrest (25.4%). Most patients (57.6%) had more than 1 indication. The overall in-hospital mortality rate was 30.5%. Mortality was 29.8% in patients with respiratory failure, 39.5% with cardiogenic shock, 46.7% with cardiac arrest, and 42.4% in those with combined diagnoses. Cardiogenic shock was associated with a significantly higher mortality rate and adjusted odds ratio 5.0 (95% CI, 1.25-27.0). Most patients (62.7%) had one or more comorbidities. CONCLUSIONS: The frequency of ECMO use across the pregnant population was low over this time period, with a mortality rate of 1 in 3 patients. Mortality was greatest in patients with cardiogenic shock. Further work is needed to understand how best to improve ECMO outcomes in pregnant patients.

Assessment of sensory block during labour epidural analgesia: a prospective cohort study to determine the influence of the direction of testing.

PURPOSE: Assessment of sensory block level during labour epidural analgesia is an essential component of clinical practice and patient safety. Nevertheless, the methods and direction of testing are not standardized. In our hospital, sensory block testing to ice is routinely used, but while some anesthesiologists test the block from a nonanesthetized to an anesthetized area, some do it in the opposite direction. It is unknown how these two different practices affect identification of the sensory block level. The objective of this study was to determine the agreement between these two practices. METHODS: We enrolled 31 patients admitted to the labour and delivery unit in a prospective cohort study. At their request, labour epidural analgesia was performed as per institutional routine. Sensory block level to ice was assessed using opposite directions by two randomly assigned independent investigators, one and two hours after the loading dose was administered. RESULTS: Sensory block levels to ice assessed from an anesthetized area to a nonanesthetized area were lower than those when assessed with the stimulus applied in the opposite direction, typically one segment lower. DISCUSSION: Given the small difference detected with both methods, it may be acceptable to use either in clinical practice. Nevertheless, the lack of standardization may have a significant impact when comparing studies involving assessment of sensory block to ice. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT03572439); registered 28 June 2018.

RéSUMé: OBJECTIF: L'évaluation du niveau de bloc sensoriel pendant l'analgésie péridurale obstétricale est une composante essentielle de la pratique clinique et de la sécurité des patientes. Néanmoins, les méthodes et l'orientation des tests ne sont pas standardisées. Dans notre hôpital, les tests à la glace des blocs sensoriels sont couramment utilisés, mais alors que certains anesthésiologistes testent le bloc d'une zone non anesthésiée à une zone anesthésiée, certains le font dans la direction opposée. Nous ne savons pas dans quelle mesure ces deux pratiques différentes affectent l'identification du niveau du bloc sensoriel. L'objectif de cette étude était de déterminer la concordance entre ces deux pratiques. MéTHODE: Nous avons recruté 31 patientes admises à l'unité obstétricale dans une étude de cohorte prospective. À leur demande, l'analgésie péridurale obstétricale a été réalisée conformément à la routine institutionnelle. Le niveau du bloc sensoriel tel que mesuré par un test à la glace a été évalué dans les deux directions par deux chercheurs indépendants assignés au hasard, une et deux heures après l'administration de la dose de charge. RéSULTATS: Les niveaux de blocs sensoriels tels que mesurés par un test à la glace évalués d'une zone anesthésiée à une zone non anesthésiée étaient inférieurs à ceux évalués lorsque le stimulus était appliqué dans la direction opposée, habituellement un segment plus bas. DISCUSSION: Compte tenu de la petite différence détectée entre les deux méthodes, il peut être acceptable d'utiliser l'une ou l'autre dans la pratique clinique. Néanmoins, le manque de standardisation peut avoir un impact significatif lors de la comparaison d'études impliquant l'évaluation du bloc sensoriel à l'aide d'un test à la glace. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT03572439); enregistrée le 28 juin 2018.

Placenta Accreta Spectrum Disorders: Knowledge Gaps in Anesthesia Care.

Placenta accreta spectrum (PAS) disorder is a potentially life-threatening condition that can occur during pregnancy. PAS puts pregnant individuals at a very high risk of major blood loss, hysterectomy, and intensive care unit admission. These patients should receive care in a center with multidisciplinary experience and expertise in managing PAS disorder. Obstetric anesthesiologists play vital roles in the peripartum care of pregnant patients with suspected PAS. As well as providing high-quality anesthesia care, obstetric anesthesiologists coordinate peridelivery care, drive transfusion-related decision making, and oversee postpartum analgesia. However, there are a number of key knowledge gaps related to the anesthesia care of these patients. For example, limited data are available describing optimal anesthesia staffing models for scheduled and unscheduled delivery. Evidence and consensus are lacking on the ideal surgical location for delivery; primary mode of anesthesia for cesarean delivery; preoperative blood ordering; use of pharmacological adjuncts for hemorrhage management, such as tranexamic acid and fibrinogen concentrate; neuraxial blocks and abdominal wall blocks for postoperative analgesia; and the preferred location for postpartum care. It is also unclear how anesthesia-related decision making and interventions impact physical and mental health outcomes. High-quality international multicenter studies are needed to fill these knowledge gaps and advance the anesthesia care of patients with PAS.

Obstetric Emergencies Requiring Rapid Response Team Activation: A Retrospective Cohort Study in a High-Risk Tertiary Care Centre.

OBJECTIVE: The purpose of this study was to better understand obstetric codes requiring rapid response team activation by examining their incidence, indications, team response, and patient outcomes. METHODS: This was a retrospective study in peripartum women who required activation of the following codes during hospitalization between January 2014 and May 2018: "Code 77 (C77)" (obstetric emergency), "Code Blue (CB)" (cardiopulmonary compromise) or "Code Omega (CO)" (massive transfusion). Hospital database and health records were searched to identify and review cases. Data on code characteristics, resuscitative measures, and maternal and neonatal outcomes were collected. RESULTS: A total of 147 codes were identified during the study period (C77, 110; CO, 25; CB 12), with an overall incidence of 1 per 203 deliveries (C77, 1:271 deliveries, CO, 1:1194 deliveries; CB, 1:2488 deliveries). Common indications for C77 were cord prolapse (33%) and fetal bradycardia (32%), and for CO and CB, postpartum hemorrhage (84%) and cardiac arrest (42%), respectively. Most codes (67%) occurred after hours. The median decision-to-delivery interval was 8 (interquartile range 5-15) minutes after C77. Emergency cesarean delivery was performed for 57% of obstetric emergencies, and general anesthesia was administered in 63% of cesarean deliveries. Maternal and neonatal mortality rates were 0.68% and 7%, respectively. Major maternal morbidity was seen in 33% of cases. Debrief was documented for 4% of codes. CONCLUSION: Rapid response team activation was required more commonly in C77 than in CO or CB. Their response time and decision-to-delivery intervals were rapid. Mortality was low; however, one-third of parturients had major morbidities. We suggest closer patient monitoring, immediate availability of resources, and appropriate documentation and debriefing.

Anesthesia-related adverse events in obstetric patients: a population-based study in Canada.

BACKGROUND: Anesthesia-related complications in obstetric patients could be catastrophic and impact the lives of both the parturient and the neonate. The objective of this study was to determine the frequency, temporal trend, and risk factors of anesthesia-related adverse events during hospitalization for delivery in Canada. METHODS: This retrospective population-based study utilized the hospitalization database of the Canadian Institute for Health Information for all parturients (gestation ≥ 20 weeks) in Canada (except Quebec) hospitalized for childbirth from April 2004 to March 2017. Complications were identified by the enhanced Canadian version of the tenth revision of the International Statistical Classification of Diseases and Related Health Problems codes. Data were summarized with descriptive statistics. Associations between hospitalizations with an anesthesia-related adverse event and patient characteristics, delivery method, and modality of anesthesia were assessed using multivariate logistic regression. RESULTS: Among 2,601,034 hospitalizations (3,194,875 interventions), 8,361 anesthesia-related adverse events occurred over a 13-year period (262 per 100,000 interventions; 95% confidence interval [CI], 256 to 267), with a significant decline over time (P < 0.001). These were two-fold and seven-fold higher per 100,000 interventions with general (488; 95% CI, 438 to 542) and general plus neuraxial (1,476; 95% CI, 1,284 to 1,689) anesthesia compared with neuraxial anesthesia alone (225; 95% CI, 219 to 230). Serious adverse events constituted 9% of all adverse events. The most common adverse event was spinal and epidural anesthesia-induced headache (6,908/8,361; 83%); the overall rate of failed or difficult intubations was low (201/8,361; 2%). Anesthesia-related events were more likely in those who had a Cesarean delivery compared with vaginal delivery (odds ratio [OR], 1.12; 95% CI, 1.06 to 1.18) and general anesthesia compared with neuraxial anesthesia (OR, 1.71; 95% CI, 1.53 to 1.93). Noteworthy associations were found between any anesthesia-related adverse events and cardiomyopathy (OR, 8.34; 95% CI, 2.59 to 26.83), eclampsia (OR, 3.11; 95% CI, 1.95 to 4.97), and obstructive sleep apnea (OR, 1.91; 95% CI, 1.66 to 2.19). CONCLUSION: The incidence of anesthesia-related adverse events in obstetric patients in Canada is low and declining. High vigilance is required in parturients undergoing Cesarean delivery, receiving general anesthesia, and those with pre-existing medical conditions.

RéSUMé: CONTEXTE: Les complications liées à l'anesthésie chez les patientes obstétricales pourraient être catastrophiques et avoir un impact tant sur la vie de la parturiente que sur celle du nouveau-né. L'objectif de cette étude était de déterminer la fréquence, la tendance temporelle et les facteurs de risque d'événements indésirables liés à l'anesthésie pendant l'hospitalisation pour accouchement au Canada. MéTHODE: Cette étude rétrospective basée sur la population a utilisé la base de données sur les hospitalisations de l'Institut canadien d'information sur la santé pour analyser les dossiers de toutes les parturientes (≥ 20 semaines de gestation) au Canada (à l'exception du Québec) hospitalisées pour accouchement entre les mois d'avril 2004 et mars 2017. Les complications ont été identifiées en suivant la version canadienne améliorée de la dixième révision des codes de la Classification statistique internationale des maladies et des problèmes de santé connexes. Les données ont été résumées à l'aide de statistiques descriptives. Les associations entre les hospitalisations comportant un événement indésirable lié à l'anesthésie et les caractéristiques de la patiente, la méthode d'accouchement et les modalités anesthésiques ont été évaluées à l'aide d'une régression logistique multivariée. RéSULTATS: Parmi les 2 601 034 hospitalisations (3 194 875 interventions), 8361 événements indésirables liés à l'anesthésie se sont produits sur une période de 13 ans (262 par 100 000 interventions; intervalle de confiance [IC] à 95 %, 256 à 267), avec une baisse significative au fil du temps (P < 0,001). Celles-ci étaient deux et sept fois plus élevées par 100 000 interventions avec une anesthésie générale (488; IC 95 %, 438 à 542) et avec une anesthésie générale plus neuraxiale (1476; IC 95 %, 1284 à 1689), respectivement, par rapport à une anesthésie neuraxiale seule (225; IC 95 %, 219 à 230). Les événements indésirables graves constituaient 9 % de tous les événements indésirables. L'événement indésirable le plus fréquent était les céphalées consécutives à l'anesthésie rachidienne et péridurale (6908/8361; 83 %); le taux global d'échecs d'intubation ou d'intubations difficiles était faible (201/8361; 2 %). Les événements liés à l'anesthésie étaient plus probables chez les parturientes ayant subi un accouchement par césarienne par rapport à un accouchement vaginal (rapport de cotes [RC], 1,12; IC 95 %, 1,06 à 1,18) et une anesthésie générale par rapport à une anesthésie neuraxiale (RC, 1,71; IC 95 %, 1,53 à 1,93). Des associations remarquables ont été notées entre tout événement indésirable lié à l'anesthésie et la cardiomyopathie (RC, 8,34; IC 95 %, 2,59 à 26,83), l'éclampsie (RC, 3,11; IC 95 %, 1,95 à 4,97) et l'apnée obstructive du sommeil (RC, 1,91; IC 95 %, 1,66 à 2,19). CONCLUSION: Au Canada, l'incidence d'événements indésirables liés à l'anesthésie chez les patientes obstétricales est faible et en baisse. Une vigilance élevée est de mise lors de la prise en charge de parturientes accouchant par césarienne, recevant une anesthésie générale et pour celles souffrant de conditions médicales préexistantes.

Management of difficult and failed intubation in the general surgical population: a historical cohort study in a tertiary care centre.

PURPOSE: The objective of this study was to describe the incidence, management, and complications of difficult and failed endotracheal intubation in a general surgical population. METHODS: This historical cohort study included all cases of difficult endotracheal intubation in general surgical patients at Mount Sinai Hospital (Toronto, ON, Canada) from 1 January 2011 to 31 December 2017. Patient charts and electronic records were reviewed to collect data on airway management and complications. Endotracheal intubation was graded as "difficult" if more than two attempts with direct laryngoscopy or if additional equipment for second or subsequent attempts was required, and "failed" if it could not be achieved despite the attempts. The primary outcome was the incidence of difficult and failed intubation. The secondary outcomes were complications, difficult airway parameters, mask ventilation, number of intubation attempts, and rescue devices including the eventually successful method. RESULTS: We identified 111 cases of difficult intubation (0.26%) and 14 cases of failed intubation (0.03%) in 42,805 surgical cases requiring endotracheal intubation over the seven-year period. The incidence was highest in 2012 (0.36%) and lowest in 2017 (0.13%). Difficulty was anticipated in 84 (76%) patients. The median (range) number of intubation attempts was 2 (2-5). Videolaryngoscopy was the eventually successful method in those with unsuccessful first attempt direct laryngoscopy (n = 91) and videolaryngoscopy (n = 17) in 71% and 77% cases, respectively. Intubation failed in 14 patients, three of whom required a surgical airway because the lungs could not be ventilated. Poor visualization of the glottis (93%) and airway bleeding (36%) were the leading causes of failed intubation. Desaturation was seen in 8%, airway bleeding in 7%, and airway edema in 6% of cases of difficult intubation. CONCLUSION: The incidences of difficult and failed intubations in our study were 2.6 and 0.3 per 1,000 surgeries requiring laryngoscopies, respectively, with a decrease over time. Videolaryngoscopy showed a high success rate as a rescue device.

RéSUMé: OBJECTIF: L'objectif de cette étude était de décrire l'incidence, la prise en charge et les complications d'une intubation endotrachéale difficile et d'un échec d'intubation dans une population chirurgicale générale. MéTHODE: Cette étude de cohorte historique a inclus tous les cas d'intubation endotrachéale difficile chez des patients de chirurgie générale à l'Hôpital Mount Sinai (Toronto, ON, Canada) du 1er janvier 2011 au 31 décembre 2017. Les dossiers papier et électroniques des patients ont été passés en revue afin de recueillir des données sur la prise en charge des voies aériennes et les complications. L'intubation endotrachéale a été classée comme « difficile ¼ si plus de deux tentatives avec laryngoscopie directe ou si du matériel supplémentaire pour la deuxième tentative ou les tentatives ultérieures était nécessaire, et « échec ¼ si elle n'avait pas pu être réalisée malgré les tentatives. Le critère d'évaluation principal était l'incidence d'intubation difficile et d'échec. Les critères d'évaluation secondaires comportaient les complications, les critères de voies aériennes difficiles, la ventilation au masque, le nombre de tentatives d'intubation et les dispositifs de sauvetage, y compris la méthode permettant finalement un succès d'intubation. RéSULTATS: Nous avons identifié 111 cas d'intubation difficile (0,26 %) et 14 cas d'échec d'intubation (0,03 %) parmi les 42 805 cas chirurgicaux nécessitant une intubation endotrachéale au cours de la période de sept ans. L'incidence était la plus élevée en 2012 (0,36 %) et la plus basse en 2017 (0,13 %). Des difficultés avaient été anticipées chez 84 (76 %) patients. Le nombre médian (intervalle) de tentatives d'intubation était de 2 (2 à 5). La vidéolaryngoscopie a été la méthode permettant le succès final de l'intubation chez les patients pour lesquels la première tentative avait échoué avec la laryngoscopie directe (n = 91) ou la vidéolaryngoscopie (n = 17), soit dans 71 % et 77 % des cas, respectivement. L'intubation a échoué chez 14 patients, dont trois ont nécessité un accès chirurgical aux voies aériennes car les poumons ne pouvaient pas être ventilés. Une mauvaise visualisation de la glotte (93 %) et des saignements des voies aériennes (36 %) étaient les principales causes d'échec de l'intubation. Une désaturation a été observée dans 8 % des cas d'intubation difficile, alors que des saignements des voies aériennes ont été observés dans 7 % et un œdème des voies aériennes dans 6 % des cas. CONCLUSION: Dans notre étude, les incidences d'intubations difficiles et d'échec étaient de 2,6 et 0,3 pour 1000 chirurgies nécessitant des laryngoscopies, respectivement, avec une diminution au fil du temps. La vidéolaryngoscopie a montré un taux de réussite élevé en tant que dispositif de sauvetage.

Incidence, morbidity, and associated factors for sepsis in women hospitalized for delivery: a nationwide retrospective observational population-based study in Canada.

PURPOSE: The objective of this research was to examine the epidemiology of maternal sepsis in Canada. METHODS: We conducted a population-based retrospective cohort study of women (≥ 20 weeks gestation) hospitalized for delivery in all Canadian hospitals (excluding Quebec) between 1 April 2004 and 31 March 2017. Data were obtained from the national Canadian Institute for Health Information database and sepsis cases were identified via International Classification of Diseases, Tenth Revision, Canada (ICD-10-CA) codes. Our primary outcome was the number of hospitalizations for delivery associated with maternal sepsis. We further explored associations between patient characteristics, obstetric procedures/conditions, medical conditions, and maternal sepsis. Associations were presented using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There were 4,183 cases of sepsis in 3,653,783 hospitalizations for delivery during the study period, with an incidence of 114 (95% CI, 111 to 118) per 100,000 hospitalizations and a mortality rate of 0.5%. Annual sepsis rates per 100,000 hospitalizations ranged from a high of 160 (95% CI, 146 to 177) in 2004 to 94 (95% CI, 83 to 106) in 2011. Highest regional rates were observed in the Territories (224 per 100,000). Severe sepsis was seen in 14% (n = 568) of all patients with sepsis, which was one or more of septic shock (15%; n = 85), organ failure (61%; n = 345), intensive care unit admission (78%; n = 443), or mortality (3%; n = 19). Multivariable models showed that postpartum hemorrhage (OR, 2.9; 95% CI, 2.7 to 3.2), Cesarean delivery (OR, 3.2; 95% CI, 3.0 to 3.5), anemia (OR, 3.9; 95% CI, 3.5 to 4.3), hysterectomy (OR, 4.9; 95% CI, 3.6 to 6.6), chorioamnionitis (OR, 7.6; 95% CI, 6.9 to 8.3), as well as cardiorespiratory, renal and liver conditions were associated with maternal sepsis. CONCLUSION: Maternal sepsis rates have been decreasing in Canada but remain higher than those in the UK and USA. Our study explored associations with maternal sepsis and shows that one in seven women with sepsis develop severe sepsis-related morbidity, which warrants risk stratification and health policy changes.

RéSUMé: OBJECTIF: L'objectif de cette étude était d'examiner l'épidémiologie du sepsis maternel au Canada. MéTHODE: Nous avons mené une étude de cohorte rétrospective basée sur la population de femmes (≥ 20 semaines de gestation) hospitalisées pour accouchement dans tous les hôpitaux canadiens excluant le Québec entre le 1er avril 2004 et le 31 mars 2017. Les données ont été obtenues à partir de la base de données nationale de l'Institut canadien d'information sur la santé et les cas de sepsis ont été identifiés au moyen des codes de la Classification internationale des maladies, dixième révision, Canada (CIM-10-CA). Notre critère d'évaluation principal était le nombre d'hospitalisations pour accouchement associées à un sepsis maternel. Nous avons également exploré les associations entre les caractéristiques des patientes, les interventions / conditions obstétricales, les conditions médicales et le sepsis maternel. Les associations ont été présentées à l'aide de rapports de cotes (RC) et d'intervalles de confiance (IC) à 95 %. RéSULTATS: Il y a eu 4183 cas de sepsis parmi les 3 653 783 hospitalisations pour accouchement au cours de la période à l'étude, avec une incidence de 114 (IC 95 %, 111 à 118) pour 100 000 hospitalisations et un taux de mortalité de 0,5 %. Les taux annuels de sepsis pour 100 000 hospitalisations variaient d'un pic de 160 (IC 95 %, 146 à 177) en 2004 à 94 (IC 95 %, 83 à 106) en 2011. Les taux régionaux les plus élevés ont été observés dans les Territoires (224 pour 100 000). Un sepsis sévère a été observé chez 14 % (n = 568) des patientes atteintes de sepsis. Cette complication s'est manifestée en choc septique (15 %; n = 85), défaillance d'organe (61 %; n = 345), admission aux soins intensifs (78 %; n = 443), ou mortalité (3 %; n = 19), ou en combinaison de ces complications. Des modèles multivariés ont montré que l'hémorragie du post-partum (RC, 2,9; IC 95 %, 2,7 à 3,2), l'accouchement par césarienne (RC, 3,2; IC 95 %, 3,0 à 3,5), l'anémie (RC, 3,9; IC 95 %, 3,5 à 4,3), l'hystérectomie (RC, 4,9; IC 95 %, 3,6 à 6,6), la chorioamnionite (RC, 7,6; IC 95 %, 6,9 à 8,3), ainsi que les affections cardiorespiratoires, rénales et hépatiques étaient associées au sepsis maternel. CONCLUSION: Les taux de sepsis maternel ont diminué au Canada, mais demeurent plus élevés qu'au Royaume-Uni et aux États-Unis. Notre étude a exploré les associations avec le sepsis maternel et montre qu'une femme sur sept atteinte de sepsis développe une morbidité sévère liée au sepsis, ce qui justifie une stratification des risques et des changements dans les politiques de santé.

Prophylactic Administration of Uterotonics to Prevent Postpartum Hemorrhage in Women Undergoing Cesarean Delivery for Arrest of Labor: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest. METHODS: In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test. RESULTS: From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group. CONCLUSION: Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01869556.

The Effects of Nitroglycerin on the Oxytocin Dose-Response Profile in Oxytocin-Desensitized and Naïve Human Myometrium: An In Vitro Study.

BACKGROUND: Nitroglycerin is used for acute reduction in uterine tone. Prolonged oxytocin exposure causes desensitization of oxytocin receptors. It is unknown if nitroglycerin exposure impacts the subsequent action of oxytocin in the setting of oxytocin receptor desensitization. This study investigated the effects of nitroglycerin on oxytocin-desensitized and oxytocin-naïve human myometrium and the subsequent response to oxytocin dose-response testing in vitro. METHODS: Myometrial samples from 17 elective cesarean deliveries were divided into strips and allocated to 1 of 4 groups: (1) oxytocin desensitized and no nitroglycerin; (2) oxytocin desensitized and nitroglycerin; (3) oxytocin naïve and nitroglycerin; and (4) oxytocin naïve and no nitroglycerin. Final analysis included 28 strips per group. Nitroglycerin groups were exposed to incremental concentrations of nitroglycerin, while no nitroglycerin groups were kept in control (physiological salt) solution. All groups then underwent oxytocin dose-response testing. Primary outcome was motility index (amplitude × frequency; grams × contractions per 10 minutes [g·c/10 min]). Secondary outcomes were amplitude (g), frequency (contractions/10 minutes), and area under the curve (g·s). All outcomes (nitroglycerin and oxytocin dose-response periods) were expressed as a percentage change from baseline. Values were log transformed, compared using regression modeling and reported as the ratio of 2 geometric means (relative difference). RESULTS: No significant difference was observed in motility index following nitroglycerin administration in oxytocin-desensitized versus oxytocin-naïve groups (relative difference = 19.0%; 95% confidence interval [CI], -32.6 to 109.9; P = .55). On oxytocin dose-response testing, motility index was highest in oxytocin-naïve and no nitroglycerin samples (group 4) (1.356 g·c/10 minutes) followed by oxytocin-naïve and nitroglycerin (group 3) (0.882 g·c/10 minutes), oxytocin-desensitized and no nitroglycerin (group 1) (0.769 g·c/10 minutes), and oxytocin-desensitized and nitroglycerin (group 2) (0.651 g·c/10 minutes) samples. Motility index was significantly reduced in group 1 vs 4 (relative difference = -43.3%; 95% CI, -66.5 to -4.1; P = .034) and group 2 vs 4 (relative difference = -52.0%; 95% CI, -70.9 to -20.8; P = .004). While in groups 3 vs 4, both amplitude (relative difference = -17.8%; 95% CI, -30.9 to -2.2; P = .27) and area under the curve (AUC; relative difference = -17.5%; 95% CI, -30.7 to -1.8; P = .030) were reduced. CONCLUSIONS: Nitroglycerin-induced relaxation was not different between oxytocin-desensitized and oxytocin-naïve human myometrial strips in vitro. However, oxytocin-induced contractility was attenuated after nitroglycerin exposure in both oxytocin-desensitized and oxytocin-naïve samples, with maximum attenuation observed in desensitized tissues. This finding warrants further clinical studies to explore uterine responsiveness to oxytocin in women with oxytocin-augmented labors after nitroglycerin administration.

The effect of morbid obesity or advanced maternal age on oxytocin-induced myometrial contractions: an in vitro study.

PURPOSE: The purpose of this study was to investigate myometrial contractility induced by oxytocin in women with advanced maternal age (AMA) and morbid obesity (MO). We hypothesized that both oxytocin-pretreated and oxytocin-naïve myometrial tissues from women of AMA and women who are MO would exhibit poor myometrial contractility compared with women that are younger and of normal body mass index (BMI). METHODS: This prospective in vitro study was conducted using myometrial samples obtained from women undergoing elective Cesarean deliveries. Three groups of patient were studied: control (≤ 35 yr; BMI, 20-24.9 kg·m-2), AMA (≥ 40 yr; BMI, 20-24.9 kg·m-2), and MO (≤ 35 yr BMI, ≥ 40 kg·m-2). Each myometrial strip was either pretreated with oxytocin 10-5 M or left in physiologic salt solution for two hours. This was followed by a dose-response testing to oxytocin (10-10 M to 10-5 M), during which contractile parameters were measured. The primary outcome was motility index (MI, amplitude × frequency) of contractions. RESULTS: The MI of contractions was reduced in oxytocin-pretreated samples when compared with their oxytocin naïve counterparts in control (estimated difference -69%; 95% confidence interval [CI], -82 to -48; P < 0.001) and AMA groups (estimated difference, -44%; 95% CI, -68 to -2; P = 0.07). The MI of contractions was not different between oxytocin naïve and oxytocin-pretreated samples from MO women (estimated difference, -26%; 95% CI, -63 to 49; P = 0.46); however, it was significantly lower in these groups compared with oxytocin-naïve samples from the control group. CONCLUSIONS: Oxytocin pre-treatment reduced myometrial contractility in AMA and control group women compared with their oxytocin-naïve counterparts, as a function of the desensitization phenomenon. Attenuated oxytocin-induced myometrial contractility in MO women in both oxytocin-pretreated and oxytocin-naïve samples suggests that these women have intrinsically reduced uterine contractile ability. TRIAL REGISTRATION: www.clinicaltrials.gov (NCT01865669; registered 28 May, 2013).

RéSUMé: OBJECTIF: L'objectif de cette recherche était d'étudier la contractilité myométriale induite par l'oxytocine chez des femmes d'âge maternel avancé (AMA) et ayant une obésité morbide (OM). Nous avons formulé l'hypothèse que les tissus de myomètre prétraités avec de l'oxytocine ainsi que les tissus naïfs d'oxytocine provenant de femmes d'AMA ou ayant une OM présenteraient une mauvaise contractilité comparativement à des femmes plus jeunes et à l'indice de masse corporelle (IMC) normal. MéTHODES: Cette étude prospective in vitro a été menée en utilisant des échantillons de myomètre prélevés sur des femmes accouchant par césarienne planifiée. Trois groupes de patientes ont été étudiés : contrôles (≤ 35 ans; IMC, 20 à 24,9 kg·m−2), AMA (≥ 40 ans; IMC, 20 à 24,9 kg·m−2) et OM (≤ 35 ans IMC, ≥ 40 kg·m−2). Chaque bandelette de myomètre a été prétraitée avec de l'oxytocine 10−5 M ou laissée dans une solution salée physiologique pendant deux heures. Cela a été suivi de tests de réponse à des doses croissantes d'oxytocine (10−10 M à 10−5 M) au cours desquels les paramètres contractiles ont été mesurés. Le critère d'évaluation principal était l'indice de motilité (IM, amplitude × fréquence) des contractions. RéSULTATS: Cet IM des contractions était diminué dans les échantillons prétraités avec l'oxytocine, comparativement à leurs équivalents naïfs d'oxytocine dans les groupes contrôles (différence estimée -69 %; intervalle de confiance [IC] à 95 % : -82 à -48; P < 0,001) et AMA (différence estimée, -44 %; IC à 95 %, -68 à -2; P = 0,07). L'IM des contractions n'était pas différent entre les échantillons naïfs d'oxytocine et les échantillons prétraités provenant de femmes ayant une OM (différence estimée, -26 %; IC à 95 %, -63 à 49; P = 0,46). Il était cependant significativement plus faible dans ces groupes comparativement aux échantillons naïfs pour l'oxytocine provenant du groupe contrôle. CONCLUSIONS: Le prétraitement à l'oxytocine a réduit la contractilité myométriale des femmes des groupes AMA et contrôle comparativement à celle des prélèvements naïfs d'oxytocine en fonction d'un phénomène de désensibilisation. L'atténuation de la contractilité myométriale induite par l'oxytocine dans les échantillons prétraités et naïfs d'oxytocine chez les femmes présentant une OM suggère que ces dernières présentent une capacité contractile intrinsèquement réduite de l'utérus. ENREGISTREMENT DE L'ESSAI CLINIQUE: www.clinicaltrials.gov (NCT01865669; enregistré le 28 mai 2013).

What does basic science tell us about the use of uterotonics?

Pharmacotherapy with uterotonics remains the mainstay of the management for post-partum haemorrhage. Clinical studies evaluating the efficacy of these drugs are fraught with confounders, which may influence uterine contractility and blood loss. For this reason, a range of techniques have been developed to study myometrial function in vitro, allowing for the comparison of various drugs in a controlled-simulated physiological environment. In this review, we focus on the main classes of uterotonic drugs and outline their molecular and physiological basis of action. We explore the evidence related to appropriate drug dosing and relative efficacy, and compare the evidence gleaned from clinical and in vitro studies. We discuss the mechanism of oxytocin desensitisation and how basic science has helped us understand this phenomenon. We also discuss the in vitro research findings for each of the main classes of uterotonic drugs that have contributed to an improved understanding of the management of post-partum haemorrhage and, ultimately, better care for mothers.