Association of chronic poststernotomy pain and health-related quality of life: a prospective cohort study.

PURPOSE: Chronic poststernotomy pain (CPSP) after cardiac surgery is multifactorial and impacts patient recovery. We aimed to evaluate the association between CPSP severity and health-related quality of life at six months after cardiac surgery. METHODS: This was a single-centre prospective cohort study of patients who underwent cardiac surgery with median sternotomy between September 2020 and March 2021. Telephone interviews were conducted at six and 12 months postoperatively using the Short Form McGill Pain Questionnaire and the EQ-5D-5L. Strength of correlation was described using Spearman's correlation coefficient. Multivariable regression analysis was used to account for confounding variables. RESULTS: A total of 252 patients responded to the six-month interview (response rate, 65%). The mean (standard deviation) age of respondents was 65 (13) yr. Twenty-nine percent of respondents (72/252) reported CPSP at six months, and 14% (41/252) reported more than mild pain (score ≥ 2/5). At 12 months, of the 89% (64/72) patients who responded, 47% (30/64) still reported pain. The strength of the correlation between pain scores and EQ-5D-5L was weak (Spearman's correlation coefficient, -0.3). Risk factors for CPSP at six months included higher pain score on postoperative day 1, history of chronic pain prior to surgery, and history of depression. Intraoperative infusion of dexmedetomidine or ketamine was associated with a reduced risk of CPSP at six months. CONCLUSION: Chronic poststernotomy pain still affects patient recovery at six and 12 months after cardiac surgery. The severity of that pain is poorly correlated with patients' quality of life. STUDY REGISTRATION: www.osf.io ( https://osf.io/52rsw ); registered 14 May 2022.

RéSUMé: OBJECTIF: La douleur chronique post-sternotomie (DCPS) après une chirurgie cardiaque est multifactorielle et a un impact sur le rétablissement des patient·es. Nous avons cherché à évaluer l'association entre la sévérité de la DCPS et la qualité de vie liée à la santé six mois après la chirurgie cardiaque. MéTHODE: Il s'agissait d'une étude de cohorte prospective monocentrique portant sur des patient·es ayant bénéficié d'une chirurgie cardiaque avec sternotomie médiane entre septembre 2020 et mars 2021. Des entrevues téléphoniques ont été menées à six et 12 mois après l'opération en se servant du questionnaire abrégé de McGill sur la douleur et de l'EQ-5D-5L. La force de corrélation a été décrite à l'aide du coefficient de corrélation de Spearman. Une analyse de régression multivariée a été utilisée pour tenir compte des variables confondantes. RéSULTATS: Au total, 252 patient·es ont répondu à l'entrevue à six mois (taux de réponse de 65 %). L'âge moyen (écart type) des répondant·es était de 65 (13) ans. Vingt-neuf pour cent des personnes répondantes (72/252) ont déclaré avoir été atteintes de DCPS à six mois, et 14 % (41/252) ont signalé une douleur plus que légère (score ≥ 2/5). À 12 mois, sur les 89 % (64/72) personnes ayant répondu, 47 % (30/64) signalaient encore de la douleur. La force de la corrélation entre les scores de douleur et l'EQ-5D-5L était faible (coefficient de corrélation de Spearman, −0,3). Les facteurs de risque de DCPS à six mois comprenaient un score de douleur plus élevé au jour 1 postopératoire, des antécédents de douleur chronique avant la chirurgie et des antécédents de dépression. Une perfusion peropératoire de dexmédétomidine ou de kétamine a été associée à une réduction du risque de DCPS à six mois. CONCLUSION: La douleur chronique post-sternotomie affecte toujours le rétablissement des patient·es six et 12 mois après la chirurgie cardiaque. La sévérité de cette douleur est faiblement corrélée à la qualité de vie des patient·es. ENREGISTREMENT DE L'éTUDE: www.osf.io ( https://osf.io/52rsw ); enregistrée le 14 mai 2022.

Development and internal validation of a multivariable risk prediction model for severe rebound pain after foot and ankle surgery involving single-shot popliteal sciatic nerve block.

BACKGROUND: Rebound pain occurs after up to 50% of ambulatory surgeries involving regional anaesthesia. To assist with risk stratification, we developed a model to predict severe rebound pain after foot and ankle surgery involving single-shot popliteal sciatic nerve block. METHODS: After ethics approval, we performed a single-centre retrospective cohort study. Patients undergoing lower limb surgery with popliteal sciatic nerve block from January 2016 to November 2019 were included. Exclusion criteria were uncontrolled pain in the PACU, use of a perineural catheter, or loss to follow-up. We developed and internally validated a multivariable logistic regression model for severe rebound pain, defined as transition from well-controlled pain in the PACU (numerical rating scale [NRS] 3 or less) to severe pain (NRS ≥7) within 48 h. A priori predictors were age, sex, surgery type, planned admission, local anaesthetic type, dexamethasone use, and intraoperative anaesthesia type. Model performance was evaluated using area under the receiver operating characteristic curve (AUROC), Nagelkerke's R2, scaled Brier score, and calibration slope. RESULTS: The cohort included 1365 patients (mean [standard deviation] age: 50 [16] yr). The primary outcome was abstracted in 1311 (96%) patients, with severe rebound pain in 652 (50%). Internal validation revealed poor model performance, with AUROC 0.632 (95% confidence interval [CI]: 0.602-0.661; bootstrap optimisation 0.021), Nagelkerke's R2 0.063, and scaled Brier score 0.047. Calibration slope was 0.832 (95% CI: 0.623-1.041). CONCLUSIONS: We show that a multivariable risk prediction model developed using routinely collected clinical data had poor predictive performance for severe rebound pain after foot and ankle surgery. Prospective studies involving other patient-related predictors are needed. CLINICAL TRIAL REGISTRATION: NCT05018104.

Noise in the operating room during induction of anesthesia: impact of a quality improvement initiative.

PURPOSE: Noise in the operating room (OR) is common and associated with negative effects on anesthesiologists, surgeons, and patient outcomes. Induction of anesthesia is among the loudest perioperative periods. Despite its critical nature, there is little data on noise levels during induction, associated patient and anesthesiologist satisfaction, and the effects of noise reduction strategies. METHODS: We conducted a two-part prospective interventional quality improvement project on the care of adult patients receiving general anesthesia for elective noncardiac surgery. For part A, we measured average and peak noise (dB[A]) levels during anesthesia induction in N = 100 cases and administered a satisfaction questionnaire to anesthesiologists. We then applied a multidisciplinary educational program to OR personnel on active noise reduction strategies and subsequently collected data during N = 109 cases in a post-intervention phase. For part B, we administered satisfaction questionnaires to N = 100 patients pre- vs postintervention, respectively. RESULTS: Median [interquartile range] noise levels throughout induction were 66.0 [62.5-68.6] dB(A) preintervention vs 63.5 [60.1-65.4] dB[A] post-intervention (Hodges-Lehmann estimator of the difference, - 2.7 dB[A]; 95% confidence interval [CI], - 4.0 to - 1.5; P < 0.001). Peak noise levels during induction were 87.3 [84.0-90.5] dB(A) preintervention and 86.2 [81.8-89.3] dB(A) postintervention (Hodges-Lehmann estimator of the difference, - 1.8 dB[A]; 95% CI, - 3.3 to - 0.3; P = 0.02). Noise-related anesthesiologist satisfaction postintervention was significantly improved in multiple domains, including assessment of noise having distracted anesthesiologists. Patient satisfaction was high pre-intervention and did not significantly improve further. CONCLUSION: In this quality improvement project, average noise levels during induction of anesthesia, anesthesiologist satisfaction, and anesthesiologists' perceived ability to perform were improved following a multidisciplinary educational program on noise reduction in the OR. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT04204785); registered 19 December 2019.

RéSUMé: OBJECTIF: Le bruit en salle d'opération (SOP) est fréquent et associé à des effets négatifs sur les anesthésiologistes, les chirurgiens et les issues des patients. L'induction de l'anesthésie est l'une des périodes périopératoires les plus bruyantes. Malgré sa nature critique, il existe peu de données sur les niveaux sonores pendant l'induction, la satisfaction des patients et des anesthésiologistes qui y est reliée, et les effets des stratégies de réduction du bruit. MéTHODE: Nous avons mené un projet prospectif et interventionnel, en deux parties, d'amélioration de la qualité sur les soins aux patients adultes recevant une anesthésie générale pour une chirurgie non cardiaque non urgente. Dans le cadre de la première partie A, nous avons mesuré les niveaux de bruit moyen et maximaux (dB[A]) pendant l'induction de l'anesthésie dans n = 100 cas et administré un questionnaire de satisfaction aux anesthésiologistes. Nous avons ensuite appliqué un programme de formation multidisciplinaire au personnel de la salle d'opération sur les stratégies de réduction active du bruit et avons ensuite recueilli des données pour n = 109 cas dans une phase post-intervention. Pour la deuxième partie B, nous avons administré des questionnaires de satisfaction à n = 100 patients pré- vs post-intervention, respectivement. RéSULTATS: Les niveaux de bruit médians [écart interquartile] tout au long de l'induction étaient de 66,0 [62,5­68,6] dB(A) avant l'intervention vs 63,5 [60,1­65,4] dB[A] après l'intervention (estimateur de Hodges-Lehmann, − 2,7 dB[A]; intervalle de confiance [IC] 95 %, − 4,0 à − 1,5; P < 0,001). Les niveaux maximaux de bruit pendant l'induction étaient de 87,3 [84,0­90,5] dB(A) avant l'intervention et de 86,2 [81,8­89,3] dB(A) après l'intervention (estimateur de Hodges-Lehmann, − 1,8 dB[A]; IC 95 %, − 3,3 à − 0,3; P = 0,02). La satisfaction des anesthésiologistes par rapport au bruit après l'intervention a été considérablement améliorée dans de nombreux domaines, y compris l'évaluation du bruit ayant distrait les anesthésiologistes. La satisfaction des patients était élevée avant l'intervention et ne s'est pas améliorée de manière significative. CONCLUSION: Dans ce projet d'amélioration de la qualité, les niveaux de bruit moyens lors de l'induction de l'anesthésie, la satisfaction des anesthésiologistes et la capacité perçue des anesthésiologistes à réaliser leurs tâches ont été améliorés à la suite d'un programme de formation multidisciplinaire sur la réduction du bruit en salle d'opération. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT04204785); enregistrée le 19 décembre 2019.

Trends in opioid dispensing after common abdominal and orthopedic surgery procedures in British Columbia: a retrospective cohort analysis.

PURPOSE: Postdischarge opioid prescriptions are reportedly much higher in Canada than in other countries. To assess potentially contributing factors, we examined trends after abdominal and orthopedic surgeries in British Columbia (BC). METHODS: Using the BC Ministry of Health's databases on physician billings, hospital discharge abstracts, and medication dispensations in community pharmacies for the period 2003-2016, we assembled a cohort of 263,056 patients who received laparoscopic appendectomy (LA, 11%), laparoscopic cholecystectomy (LC, 30%), open inguinal or femoral hernia repair (IHR, 20%), total hip arthroplasty (THA, 18%), or total knee arthroplasty (TKA, 22%). Adjusting for covariates using generalized linear modeling, we measured trends in percentages of patients dispensed opioids postdischarge (opioid rate) within 30 days after surgery, by surgery type, opioid type, prior use, surgeon, and trends in morphine milligram equivalents of first dispensations (MME) with 95% confidence intervals (CI). RESULTS: Opioid dispensation rates rose steadily. Mean annual increases were 1.7% in LA; 1.3% in LC; 0.8% in IHR; 0.9% in THA; and 0.8% in TKA. By 2016, rates were 69% in LA; 76% in LC; 81% in IHR; 88% in THA; and 94% in TKA. Codeine dispensations fell 2.4% (abdominal) and 3.1% (orthopedic) per year while tramadol dispensations increased 3.6% (abdominal) and 1.7% (orthopedic). Hydromorphone dispensations increased 2.9% per year (orthopedic); oxycodone was level at 22% between 2007 and 2014, but then fell. The mean MME rose 8 mg⋅yr-1 (95% CI, 7 to 9) (abdominal) and 61 mg⋅yr-1 (95% CI, 58 to 64) (orthopedic). Variation in rates was greater among abdominal than orthopedic surgeons. CONCLUSION: Rising opioid dispensation rates, together with shifts to prescribing higher MME opioids, doubled MME per patient in first dispensations postdischarge after abdominal or orthopedic surgery from 2003 to 2016 in BC.

RéSUMé: OBJECTIF: Les ordonnances d'opioïdes après le congé seraient beaucoup plus élevées au Canada que dans d'autres pays. Afin d'évaluer les facteurs contributifs potentiels, nous avons examiné les tendances après les chirurgies abdominales et orthopédiques en Colombie-Britannique (C.-B.). MéTHODE: En utilisant les bases de données du ministère de la Santé de la Colombie-Britannique de facturation des médecins, les résumés des congés d'hôpital et les délivrances de médicaments dans les pharmacies communautaires pour la période 2003-2016, nous avons regroupé une cohorte de 263 056 patients ayant bénéficié d'une appendicectomie par laparoscopie (AL, 11 %), d'une cholécystectomie par laparoscopie (CL, 30 %), d'une réparation ouverte de hernie inguinale ou fémorale (RHI, 20 %), d'une arthroplastie totale de la hanche (ATH, 18 %) ou d'une arthroplastie totale du genou (ATG, 22 %). En tenant compte des covariables à l'aide d'une modélisation linéaire généralisée, nous avons mesuré les tendances dans les pourcentages de patients ayant reçu des opioïdes après leur congé (taux de délivrance d'opioïdes) dans les 30 jours suivant leur chirurgie, par type de chirurgie, type d'opioïde, utilisation antérieure, chirurgien et tendances des équivalents de morphine en milligrammes (EMM) des premières délivrances avec des intervalles de confiance (IC) à 95 %. RéSULTATS: Les taux de délivrance d'opioïdes ont augmenté de manière constante. Les augmentations annuelles moyennes étaient de 1,7 % pour les AL, 1,3 % pour les CL, 0,8 % pour les RHI, 0,9 % pour les ATH, et 0,8 % pour les ATG. En 2016, les taux étaient de 69 % pour les AL, 76 % pour les CL, 81 % pour les RHI, 88 % pour les ATH, et 94 % pour les ATG. Les dispenses de codéine ont chuté de 2,4 % (chirurgie abdominale) et de 3,1 % (chirurgie orthopédique) par année, tandis que les délivrances de tramadol ont augmenté de 3,6 % (chirurgie abdominale) et de 1,7 % (chirurgie orthopédique). Les délivrances d'hydromorphone ont augmenté de 2,9 % par année (orthopédie); l'oxycodone était à 22 % entre 2007 et 2014, mais a ensuite diminué. Les EMM moyens ont augmenté de 8 mg·an-1 (IC 95 %, 7 à 9) (chirurgie abdominale) et de 61 mg·an-1 (IC 95 %, 58 à 64) (chirurgie orthopédique). La variation des taux était plus importante parmi les chirurgiens abdominaux que chez les chirurgiens orthopédistes. CONCLUSION: L'augmentation des taux de délivrance d'opioïdes, ainsi que le passage à une prescription d'opioïdes plus élevés en EMM, ont doublé les EMM par patient dans les premières délivrances après leur congé après une chirurgie abdominale ou orthopédique de 2003 à 2016 en Colombie-Britannique.

Opioid dispensing after Cesarean delivery in British Columbia: a historical cohort analysis from 2004 to 2019.

PURPOSE: To describe postdischarge opioid dispensing after Cesarean delivery (CD) in 49 hospitals in British Columbia (BC) and assess opportunities for opioid stewardship. METHODS: Using the BC Ministry of Health's Hospital Discharge Abstract Database, we linked 135,725 CDs performed in 2004-2016 and 30,919 CDs performed in 2017-2019 (length of stay ≤ four days) by deidentified Personal Health Numbers to data on medications dispensed from all BC community pharmacies (PharmaNet). We excluded patients with cancer and those to whom opioids have been dispensed in the year before. We measured trends in annual percentages of patients dispensed opioids within seven days (opioid rate), with 95% confidence intervals (CIs), stratified by hospital and opioid type, adjusted for length of stay, and for autocorrelation within hospital using generalized linear modeling. RESULTS: The opioid dispensation rate dropped from 31% (95% CI, 30 to 33) in 2004 to 16% (95% CI, 15 to 17) in 2016, where it remained through 2019. Five hospitals showed steep reductions from over 40% to under 10% within two to three years, but in most hospitals the opioid dispensation rate decreased slowly-11 had little reduction and three showed increases. Codeine dispensing dropped from 31% in 2004-2008 by 4% per year, while tramadol and hydromorphone dispensing rose. After 2015, rates were stable (hydromorphone, 8%; tramadol, 6%; codeine, 3%; and oxycodone, 0.5%). CONCLUSION: After Health Canada's 2008 warning against codeine use by breastfeeding mothers, post-CD opioid dispensing declined disjointedly across BC hospitals. Rates did not decrease further after the opioid overdose epidemic was declared a public health emergency in BC in 2016. The present study highlights opportunities for quality improvement and opioid stewardship through monitoring using administrative databases.

RéSUMé: OBJECTIF: Décrire la délivrance d'opioïdes après le congé après un accouchement par césarienne dans 49 hôpitaux de la Colombie-Britannique (C.-B.) et évaluer les occasions de régulation des opioïdes. MéTHODE: À l'aide de la base de données sur les congés des patients du ministère de la Santé de la Colombie-Britannique, nous avons relié 135 725 accouchements par césarienne réalisés en 2004-2016 et 30 919 accouchements par césarienne réalisés en 2017-2019 (durée de séjour ≤ quatre jours) en utilisant les numéros de carte santé personnels dépersonnalisés aux données sur les médicaments délivrés par toutes les pharmacies communautaires de la Colombie-Britannique (PharmaNet). Nous avons exclu les patientes atteintes de cancer et celles à qui des opioïdes avaient été délivrés l'année précédente. À l'aide d'une modélisation linéaire généralisée, nous avons mesuré les tendances en pourcentages annuels de patientes ayant reçu des opioïdes dans les sept jours (taux d'opioïdes), avec des intervalles de confiance (IC) à 95 %, stratifiés par hôpital et par type d'opioïdes, ajustés en fonction de la durée de séjour et des autocorrélations entre des taux de chaque hôpital. RéSULTATS: Le taux de délivrance d'opioïdes est passé de 31 % (IC 95 %, 30 à 33) en 2004 à 16 % (IC 95 %, 15 à 17) en 2016, où il est resté jusqu'en 2019. Cinq hôpitaux ont montré des réductions importantes, passant de plus de 40 % à moins de 10 % en deux à trois ans, mais dans la plupart des hôpitaux, le taux de délivrance d'opioïdes a diminué lentement ­ 11 ont affiché une faible réduction et trois ont montré des augmentations. La délivrance de codéine a diminué de 4 % par année, à partir de 31 % en 2004-2008, tandis que la délivrance de tramadol et d'hydromorphone a augmenté. Après 2015, les taux étaient stables (hydromorphone, 8 %; tramadol, 6 %; codéine, 3 %; et oxycodone, 0,5 %). CONCLUSION: Suite à la mise en garde de Santé Canada en 2008 contre la consommation de codéine par les mères qui allaitent, la délivrance d'opioïdes post-césarienne a diminué de façon inconstante dans les hôpitaux de Colombie-Britannique. Les taux n'ont pas diminué davantage après que l'épidémie de surdose d'opioïdes a été déclarée urgence de santé publique en Colombie-Britannique en 2016. La présente étude met en évidence les possibilités d'amélioration de la qualité et de régulation des opioïdes en procédant à une surveillance via les bases de données administratives.

A new hypertonic saline assay for analgesic screening in mice: effects of animal strain, sex, and diurnal phase.

PURPOSE: There exists a pressing need for the identification of novel analgesics. We recently reported on a new preclinical assay for rapid analgesic screening based on intraplantar (i.pl.) injection of 10% hypertonic saline (HS) in female outbred (CD-1) mice. Herein, we characterized the HS assay's performance in inbred (C57BL/6) mice, sensitivity to sex differences, and effects of diurnal rhythm phase. METHODS: In randomized, controlled, blinded in vivo animal experiments, we studied nociceptive responses induced by i.pl. HS in C57BL/6 (vs CD-1) mice of both sexes (n = 240) and determined diurnal rhythm phase effects in female animals. We established the HS assay's sensitivity to morphine by constructing dose-response curves and calculating half-maximal inhibitory doses (ID50s). RESULTS: The injection of i.pl. HS produced nociceptive (licking and biting) responses in all C57BL/6 mice tested. In both C57BL/6 and CD-1 mice, the mean (95% confidence interval [CI]) response magnitudes were greater in females vs males (C57BL/6: 87 sec [64 to 110] vs 45 sec [29 to 61]; difference in means, 42 sec; 95% CI, 17 to 68; P < 0.001; n = 10/group; CD-1: 110 sec [95 to 126] vs 53 sec [32 to 74]; difference in means, 57 sec; 95% CI, 34 to 79; P < 0.001; n = 10/group). The mean (95% CI) nociceptive responses were greater at 24:00 hr than at 12:00 hr in C57BL/6 mice (64 sec [40 to 88] vs 37 sec [24 to 51]; difference in means, 27 sec; 95% CI, 7 to 47; P = 0.007; n = 10/group), but not in CD-1 mice (P = 0.97). Intravenous morphine dose-dependently attenuated nociceptive responses of both C57BL/6 and CD-1 mice (ID50, 0.6 and 2.5 mg·kg-1, respectively; P = 0.41). CONCLUSION: These findings in inbred and outbred mice solidify the utility of the HS assay as an effective, rapid, robust, and versatile preclinical tool for analgesic screening.

RéSUMé: OBJECTIF: Il existe un besoin impérieux d'identification de nouveaux analgésiques. Nous avons récemment publié les conclusions d'un nouveau test préclinique portant sur le dépistage analgésique rapide basé sur l'injection intraplantaire (i.pl.) d'une solution saline hypertonique à 10 % (HS) chez des souris femelles croisées (CD-1). Dans notre présente étude, nous avons caractérisé la performance du test de HS chez des souris consanguines (C57BL/6), la sensibilité aux différences de sexe, et les effets des phases de rythme diurne. MéTHODE: Dans le cadre d'expériences animales in vivo en aveugle randomisées contrôlées, nous avons étudié les réponses nociceptives induites par une i.pl. de HS chez des souris C57BL/6 (vs CD-1) des deux sexes (n = 240) et déterminé les effets des phases du rythme diurne chez les animaux femelles. Nous avons établi la sensibilité du test HS à la morphine en construisant des courbes de dose-réponse et en calculant des doses inhibitrices semi-maximales (DI50). RéSULTATS: L'injection i.pl. de HS a produit des réponses nociceptives (léchage et morsure) chez toutes les souris C57BL/6 testées. Chez les souris C57BL/6 et CD-1, les magnitudes de réponse moyenne [intervalle de confiance (IC) 95 %] étaient plus élevées chez les femelles que chez les mâles (C57BL/6 : 87 [64 à 110] vs 45 [29 à 61] sec; différence de moyennes, 42 sec; IC 95 %, 17 à 68; P < 0,001; n = 10/groupe; CD-1: 110 [95 à 126] vs 53 [32 à 74] sec; différence de moyennes, 57 sec; IC 95 %, 34 à 79; P < 0,001; n = 10/groupe). Les réponses nociceptives moyennes [IC 95 %] étaient plus importantes à minuit (24 h) qu'à midi (12 h) chez les souris C57BL/6 (64 [40 à 88] sec vs 37 [24 à 51] sec; différence de moyennes, 27 sec; IC 95 %, 7 à 47; P = 0,007; n = 10/groupe), mais pas chez les souris CD-1 (P = 0,97). La morphine intraveineuse a atténué de façon dose-dépendante les réponses nociceptives chez les souris C57BL/6 et CD-1 (DI50, 0,6 et 2,5 mg·kg−1, respectivement; P = 0,41). CONCLUSION: Ces résultats chez les souris croisées et consanguines appuient l'utilité du test de HS comme un outil préclinique efficace, rapide, robuste et polyvalent pour le dépistage analgésique.

A Single Prophylactic Dose of Ondansetron Given at Cessation of Postoperative Propofol Sedation Decreases Postoperative Nausea and Vomiting in Cardiac Surgery Patients: A Randomized Controlled Trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common occurrence after cardiac surgery. However, in contrast to other surgical populations, routine PONV prophylaxis is not a standard of care in cardiac surgery. We hypothesized that routine administration of a single prophylactic dose of ondansetron (4 mg) at the time of stopping postoperative propofol sedation before extubation in the cardiac surgery intensive care unit would decrease the incidence of PONV. METHODS: With institutional human ethics board approval and written informed consent, we conducted a randomized controlled trial in patients ≥19 years of age with no history of PONV undergoing elective or urgent cardiac surgery procedures requiring cardiopulmonary bypass. The primary outcome was the incidence of PONV in the first 24 hours postextubation, compared by the χ test. Secondary outcomes included the incidence and times to first dose of rescue antiemetic treatment administration, the incidence of headaches, and the incidence of ventricular arrhythmias. RESULTS: PONV within the first 24 hours postextubation occurred in 33 of 77 patients (43%) in the ondansetron group versus 50 of 82 patients (61%) in the placebo group (relative risk, 0.70 [95% confidence interval {CI}, 0.51-0.95]; absolute risk difference, -18% [95% CI, -33 to -2]; number needed to treat, 5.5 [95% CI, 3.0-58.4]; χ test, P = .022). Kaplan-Meier "survival" analysis of the times to first rescue antiemetic treatment administration over 24 hours indicated that patients in the ondansetron group fared better than those in the placebo group (log-rank [Mantel-Cox] test; P = .028). Overall, 32 of 77 patients (42%) in the ondansetron group received rescue antiemetic treatment over the first 24 hours postextubation versus 47 of 82 patients (57%) in the placebo group (relative risk, 0.73 [95% CI, 0.52-1.00]; absolute risk difference, -16% [95% CI, -31 to 1]); P = .047. There were no significant differences between the groups in the incidence of postoperative headache (ondansetron group, 5 of 77 patients [6%] versus placebo group, 4 of 82 patients [5%]; Fisher exact test; P = .740) or ventricular arrhythmias (ondansetron group, 2 of 77 patients [3%] versus placebo group, 4 of 82 patients [5%]; P = .68). CONCLUSIONS: These findings support the routine administration of ondansetron prophylaxis at the time of discontinuation of postoperative propofol sedation before extubation in patients following cardiac surgery. Further research is warranted to optimize PONV prophylaxis in cardiac surgery patients.

Tissue damage in the heart after cardiac arrest induced by asphyxia and hemorrhage in newborn pigs.

BACKGROUND: Asphyxia of newborns is a severe and frequent challenge of the peri- and postnatal period. METHODS: Forty-four neonatal piglets underwent asphyxia and hemorrhage (AH), followed by resuscitation with blood or crystalloid transfusion. In this study, 15 piglets (blood n = 9, NaCl n = 6, mean age 31 h) were randomly chosen. Four hours after return of spontaneous circulation, heart tissue and blood were collected. Analyses of heart fatty acid binding protein (HFABP), cardiac troponin I (TnI) levels, and activation of the complement system were performed. Histological staining for connexin 43 (Cx43) and complement C5a receptor 1 (C5aR1) was performed. RESULTS: Following AH, systemic elevation of cardiac TnI and HFABP revealed cardiac damage in both groups. Systemic activation of the complement system and the appearance of extracellular histones in plasma of the blood transfusion group were observed. The Cx43 was translocated from the intercalated discs to the cytosol after AH. Cardiac glycogen concentration was reduced in both groups. A significant reduction of C5aR1 in the left ventricle and a significant elevation of the heart injury score were investigated after blood transfusion. CONCLUSION: AH leads to alteration of the heart, particularly in Cx43 and glycogen reserves, as well as local inflammation.

Paper-based 3D printing of anthropomorphic CT phantoms: Feasibility of two construction techniques.

OBJECTIVES: To develop and evaluate methods for assembling radiopaque printed paper sheets to realistic patient phantoms for CT dose and image quality testing. METHODS: CT images of two patients were radiopaque printed with aqueous potassium iodide solution (0.6 g/ml) on paper. Two methods were developed for assembling the paper sheets to head and neck phantoms. (1) Printed sheets were fed to a paper-based 3D printer along with corresponding 3D printable STL files. (2) Paper stacks of 5-mm thickness were glued with toner, cut to the patient shape and assembled to a phantom. In a sample application study, both phantoms were examined with five different tube current settings. Images were reconstructed using filtered-back projection (FBP) and iterative reconstruction (AIDR 3D) with three strength levels. Dose length product (DLP), signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNRs) were analysed. Data were analysed using 2-way analysis of variance (ANOVA). RESULTS: Both methods achieved anthropomorphic phantoms with detailed patient anatomy. The 3D printer yielded a precise reproduction of the external patient shape, but caused visible glue artefacts. Gluing with toner avoided these artefacts and yielded more flexibility with regard to phantom size. In the sample application study, non-inferior SNR and CNR and up to 83.7% lower DLP were achieved on the phantoms with AIDR 3D compared with FBP. CONCLUSIONS: Two methods for assembling radiopaque printed paper sheets to phantoms of individual patients are presented. The sample application demonstrates potential for simulation of patient imaging and systematic CT dose and image quality assessment. KEY POINTS: • Two methods were developed to create realistic CT phantoms of individual patients from radiopaque printed paper sheets. • Analysis of five tube current and four reconstruction settings on two radiopaque 3D printed patient phantoms yielded non-inferior SNR and CNR and up to 83.7% lower dose with iterative reconstruction in comparison with filtered back projection. • Radiopaque 3D printed phantoms can simulate patients and allow systematic analysis of CT dose and image quality parameters.

Effect of General Anaesthesia versus Conscious Sedation on Clinical and Procedural Outcome in Patients Undergoing Endovascular Stroke Treatment: A Matched-Pair Analysis.

INTRODUCTION: General anaesthesia (GA) during mechanical thrombectomy (MT) might lead to an inferior clinical outcome compared to conscious sedation (CS). It was hypothesised that using CS might avoid a critical drop in cerebral perfusion, shorten the time of the intervention and therefore might result in better clinical outcome. In this study, we compared the procedural and clinical results of patients who underwent MT under GA or CS at two tertiary neuro-vascular centres on the basis of a matched-pair analysis. METHODS: Using a matched-pair approach, we compared the data of 56 patients that were treated under CS at centre A (n = 28) with selected patients who were treated under GA at the centre B (n = 28). Patients were matched for age, sex, site of vessel occlusion, NIHSS at admission (±3 points), time from symptom onset to initial stroke imaging, intravenous-lysis and co-morbidities. All patients had an ASPECT-score of ≥8. To exclude the effect of technical failures, only patients with successful recanalization of the occluded vessel (TICI 2b and 3) were included into the study. The primary endpoint was the proportion of patients with early good clinical outcome after MT, defined by a modified Ranking Scale (mRS)-score ≤2 at discharge. Secondary endpoints were the time from symptom onset to the start of the procedure, the duration of the procedure and the rate of procedural complications. RESULTS: There were no differences concerning gender, age, the site of vessel occlusion and the degree of stroke severity at baseline. The proportion of patients with an early good clinical outcome (mRS ≤2 at discharge) was 60.4% (17/28) in both groups. The time from symptom onset to the start of the procedure was shorter at centre B, while the duration of the procedure was significantly faster at A, resulting in an overall time from symptom onset to complete recanalization of 152.2 ± 68.0 min for patients treated at centre A and 171.1 ± 43.5 min for patients at centre B (ns). CONCLUSION: Our study revealed no differences in the investigated clinical outcome for patients undergoing endovascular stroke treatment under GA versus CS.

Repeated Testing With the Hypertonic Saline Assay in Mice for Screening of Analgesic Activity.

BACKGROUND: In vivo animal assays are a cornerstone of preclinical pain research. An optimal stimulus for determining the activity of potential analgesics would produce responses of a consistent magnitude on repeated testing. Intraplantar (i.pl.) injection of hypertonic saline (HS) in mice produces robust nociceptive responses to different analgesics, without evidence of tissue damage. Here, we investigated whether the nociceptive response is changed by repeating the injection at different times and sites in a mouse and whether it is attenuated by morphine. METHODS: We conducted randomized and blinded experiments to assess responses to repeated i.pl. 10% HS in female CD-1 mice. An injection of HS was followed by a second injection into the same hind paw at 4 hours, 24 hours, or 7 days. A separate group of mice each received i.pl. injections at 5, 10, and 15 days. In 2 independent experiments, 30 minutes after initial HS injections in the ipsilateral hind paw, mice received HS injection into the contralateral hind paw or ipsilateral forepaw. The ability of morphine to block the nociceptive responses was examined by injecting morphine at 5-day intervals. RESULTS: Repeated injection of HS did not alter the responses at 4 hours (84 vs 75 seconds; mean difference [95% CI], -9 [-40 to 23]; P = .6), 24 hours (122 vs 113 seconds; -6 [-24 to 12]; P = .5), or 7 days (112 vs 113 seconds; -0.3 [-12 to 11]; P = .95) or at multiple injections (day 0, 122 seconds vs day 5, 121 seconds; -0.3 [-28 to 27], P > .99; day 10, 118 seconds; 2.5 [-36 to 41], P = .99; day 15, 119 seconds; 2 [-36 to 38], P = .99). A previous hind paw injection did not change the responses of the contralateral hind paw (right, 93 seconds versus left, 96 seconds; -3 [-20 to 13], P = .7) or of the ipsilateral forepaw (forepaw after HS, 146 seconds versus forepaw after 0.9% saline, 149 seconds; -3 [-28 to 22], P = .8). Morphine dose-dependently attenuated HS responses (control, 94 seconds vs 4 mg/kg, 66 seconds; 29 [-7 to 64], P = .12; vs 10 mg/kg, 27 seconds; 67 [44-90], P < .0001; 4 vs 10 mg/kg, 67 [44-90], P = .03). CONCLUSIONS: The repetition of i.pl. HS produces consistent reproducible responses without tissue damage. This results in efficient, rapid detection of analgesic activity, reducing the number of animals required.

Prevalence, clinical characteristics, and prognosis of GATA2-related myelodysplastic syndromes in children and adolescents.

Germline GATA2 mutations cause cellular deficiencies with high propensity for myeloid disease. We investigated 426 children and adolescents with primary myelodysplastic syndrome (MDS) and 82 cases with secondary MDS enrolled in 2 consecutive prospective studies of the European Working Group of MDS in Childhood (EWOG-MDS) conducted in Germany over a period of 15 years. Germline GATA2 mutations accounted for 15% of advanced and 7% of all primary MDS cases, but were absent in children with MDS secondary to therapy or acquired aplastic anemia. Mutation carriers were older at diagnosis and more likely to present with monosomy 7 and advanced disease compared with wild-type cases. For stratified analysis according to karyotype, 108 additional primary MDS patients registered with EWOG-MDS were studied. Overall, we identified 57 MDS patients with germline GATA2 mutations. GATA2 mutations were highly prevalent among patients with monosomy 7 (37%, all ages) reaching its peak in adolescence (72% of adolescents with monosomy 7). Unexpectedly, monocytosis was more frequent in GATA2-mutated patients. However, when adjusted for the selection bias from monosomy 7, mutational status had no effect on the hematologic phenotype. Finally, overall survival and outcome of hematopoietic stem cell transplantation (HSCT) were not influenced by mutational status. This study identifies GATA2 mutations as the most common germline defect predisposing to pediatric MDS with a very high prevalence in adolescents with monosomy 7. GATA2 mutations do not confer poor prognosis in childhood MDS. However, the high risk for progression to advanced disease must guide decision-making toward timely HSCT.

An Intraplantar Hypertonic Saline Assay in Mice for Rapid Screening of Analgesics.

BACKGROUND: Development of new analgesics is limited by shortcomings of existing preclinical screening assays such as wide variations in response, suitability for a narrow range of analgesics, and propensity to induce tissue damage. Our aim was to determine the feasibility of a new in vivo animal assay as an analgesic screen based on nociceptive responses (licking and biting) after intraplantar (i.pl.) injection of hypertonic saline (HS) in mice. METHODS: With approval from the Institutional Animal Care Committee, we conducted a randomized, investigator-blinded in vivo study in adult CD-1 mice. We first studied the concentration-response relationship, time course, and sex difference of animals' nociceptive responses to HS. Subsequently, we assessed the screening ability of the HS assay to detect a range of established analgesics belonging to different classes. Finally, we performed histopathologic studies to assess potential tissue damage. RESULTS: The response produced by i.pl. HS was greater and longer in female than in male mice. The responses to HS were concentration dependent with minimal variance. Ten percent HS evoked a maximal response within the first 5 minutes. Morphine dose-dependently attenuated animals' nociceptive responses (1-10 mg/kg intraperitoneally [i.p.]). The peripherally restricted µ-opioid receptor agonist, loperamide, reduced nociceptive responses when injected locally (30-100 µg/paw, i.pl.) but not systemically (1-10 mg/kg, i.p.). Acetylsalicylic acid (300 mg/kg, i.p.), naproxen (150 mg/kg, i.p), and acetaminophen (300 mg/kg, i.p.) all decreased nociceptive responses, as did i.pl. coinjections of lidocaine (0.003%-1%) with 10% HS. Histopathologic assessment revealed no tissue damage due to HS. CONCLUSIONS: The i.pl. HS assay is easily performed, rapidly detects standard analgesics, and produces minimal animal suffering without tissue damage. We propose this assay as a useful addition to the armamentarium of existing preclinical analgesic screens.