Association Between Intraoperative Noradrenaline Infusion and Outcomes in Older Adult Patients Undergoing Major Non-Cardiac Surgeries: A Retrospective Propensity Score-Matched Cohort Study.

Background: Noradrenaline (NA) is commonly used intraoperatively to prevent fluid overload and maintain hemodynamic stability. Clinical studies provided inconsistent results concerning the effect of NA on postoperative outcomes. As aging is accompanied with various diseases and has the high possibility of the risk for postoperative complications, we hypothesized that intraoperative NA infusion in older adult patients undergoing major non-cardiac surgeries might potentially exert adverse outcomes. Methods: In this retrospective propensity score-matched cohort study, older adult patients undergoing major non-cardiac surgeries were selected, 1837 receiving NA infusion during surgery, and 1072 not receiving NA. The propensity score matching was conducted with a 1:1 ratio and 1072 patients were included in each group. The primary outcomes were postoperative in-hospital mortality and complications. Results: Intraoperative NA administration reduced postoperative urinary tract infection (OR:0.124, 95% CI:0.016-0.995), and had no effect on other postoperative complications and mortality, it reduced intraoperative crystalloid infusion (OR:0.999, 95% CI:0.999-0.999), blood loss (OR: 0.998, 95% CI: 0.998-0.999), transfusion (OR:0.327, 95% CI: 0.218-0.490), but increased intraoperative lactate production (OR:1.354, 95% CI:1.051-1.744), and hospital stay (OR:1.019, 95% CI:1.008-1.029). Conclusion: Intraoperative noradrenaline administration reduces postoperative urinary tract infection, and does not increase other postoperative complications and mortality, and can be safely used in older adult patients undergoing major non-cardiac surgeries.

Adverse Events of Peripherally Administered Norepinephrine During Surgery: A Prospective Multicenter Study.

BACKGROUND: Perioperative treatment of hypotension by intravenous administration of norepinephrine in a peripheral vein can lead to adverse events, for example, tissue necrosis. However, the incidence and severity of adverse events during perioperative administration are unknown. METHODS: This was a prospective observational study conducted at 3 Swedish hospitals from 2019 to 2022. A total of 1004 patients undergoing surgery, who met the criteria for perioperative peripheral norepinephrine administration, were included. The infusion site was inspected regularly. If swelling or paleness of skin was detected, the infusion site was changed to a different peripheral line. Systolic blood pressure and pulse frequency were monitored during the infusion time and defined as adverse events at >220 mm Hg and <40 beats•min -1 . In case of adverse events, patients were observed for up to 48 hours. The primary outcome was prevalence of extravasation, defined as swelling around the infusion site. Secondary outcomes were all types of adverse events and associations between predefined clinical variables and risk of adverse events. RESULTS: We observed 2.3% (95% confidence interval [CI], 1.4%-3.2%) extravasation of infusion and 0.9% (95% CI, 0.4%-1.7%) bradycardia. No cases of tissue necrosis or severe hypertension were detected. All adverse events had dissipated spontaneously within 48 hours. Proximal catheter placement was associated with more adverse events. CONCLUSIONS: Extravasation of peripherally administrated norepinephrine in the perioperative period occurred at similar rates as in previous studies in critically ill patients. In our setting, where we regularly inspected the infusion site and shifted site in case of swelling or paleness of skin, we observed no case of severe adverse events. Given that severe adverse events were absent, the potential benefit of this preventive approach requires confirmation in a larger population.

A randomized open label, parallel-group study to evaluate the hemodynamic effects of Cafedrine/Theodrenaline vs Noradrenaline in the treatment of intraoperative hypotension after induction of general anesthesia: the "HERO" study design and rationale.

OBJECTIVE: Intraoperative arterial hypotension (IOH) is associated with poor patient outcome. This study aims to compare the hemodynamic effects of Cafedrine/Theodrenaline (C/T) and Noradrenaline (NA) for the treatment of hypotension in patients who develop IOH after anesthesia induction. RESEARCH DESIGN AND METHODS: This is a national, randomized, parallel-group, multicenter, and open-label study. Adult patients (≥50 years, ASA-classification III-IV) who undergo elective surgery will be included. When IOH (MAP <70 mmHg) develops, C/T or NA will be given as a bolus injection ("bolus phase", 0-20 min after initial application) and subsequently as continuous infusion ("infusion phase", 21-40 min after initial application) to achieve MAP = 90 mmHg. Hemodynamic data are captured in real time by advanced hemodynamic monitoring. RESULTS: Primary endpoints, i.e. the treatment-related difference in average mean arterial pressure (MAP) during the "infusion phase" and the treatment-related difference in average cardiac index during the "bolus phase" are assessed (fixed-sequence method). Non-inferiority of C/T compared to NA in achieving 90 mmHg (MAP) when applied as continuous infusion is hypothesized. In addition, superiority of C/T over NA, applied as bolus injection, in increasing cardiac index is postulated. It is estimated that 172 patients are required to establish statistical significance with a power of 90%. After adjusting for ineligibility and dropout rate, 220 patients will be screened. CONCLUSION: This clinical trial will yield evidence for marketing authorization of C/T applied as continuous infusion. Additionally, the effects of C/T compared to NA on cardiac index will be assessed. First results of the "HERO"-study are expected in 2024. DRKS identifier: DRKS00028589. EudraCT identifier: 2021-001954-76.

Adverse effects related with norepinephrine through short peripheral venous access: Scoping review.

Peripheral administration of norepinephrine is restricted due to the association of extravasation with tissue necrosis. METHOD: Scoping review with the objective of describing the adverse effects related to the administration of norepinephrine through short peripheral venous access and the characteristics of drug administration in patients hospitalized in ICU, surgery, and emergency services. RESULTS: 12 studies with heterogeneous characteristics by size and type of population were included. The proportion of complications associated with peripheral norepinephrine administration was less than 12% in observational studies and it was less than 2% in those that used doses less than 0.13µg/kg/min, and concentrations less than 22.3µg/mL. The main associated complication was extravasation and there were no cases of tissue necrosis at the venipuncture site, some extravasation cases were treated with phentolamine, terbutaline or topical nitroglycerin. The drug administration time ranged between 1 and 528hours with a weighted mean of 2.78h. CONCLUSION: The main adverse effect was extravasation, no additional complications occurred, phentolamine and terbutaline seem to be useful, and its availability is a necessity. It is essential for the nursing staff to carry out a close assessment and comprehensive care in patients receiving norepinephrine by peripheral route.

Clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock.

To analyze the clinical efficacy and safety of norepinephrine combined with ulinastatin in the treatment of septic shock. 100 patients with septic shock treated in our institution from May 2019 to May 2021 were recruited and randomly assigned to receive either norepinephrine (control group) or norepinephrine plus ulinastatin (experimental group) according to the treatment scheme. The treatment efficacy, time for shock improvement, intensive care unit (ICU) stay, total hospital stay, in-hospital mortality, 30-day survival, and changes in inflammatory factors (plasma C-reactive protein (CRP), serum lactic acid (LAC), serum procalcitonin (PCT), and interleukin-10 (IL-10)) before and after treatment were analyzed, and the sequential organ failure scores of the two groups were compared. The experimental group exhibited superior performance with respect to efficacy, ICU stays, and total hospital stay, in-hospital mortality to the control group (all P<0.05). After treatment, the experimental group presented lower levels of CRP, LAC, PCT and IL-10 and higher SOFA scores than the control group (P<0.05). Norepinephrine plus ulinastatin achieved remarkable results in the treatment of septic shock, improving the treatment efficiency, shortening the time for shock improvement and hospitalization, reducing hospital mortality, driving down the expression of inflammatory factors and enhancing the survival of patients, with high safety.

Neurodevelopmetal effects of maternal blood pressure management with noradrenaline during general anaesthesia for nonobstetric surgery in the pregnant rabbit model.

In pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, the rationale being to maintain uterine perfusion pressure and thereby uterine blood flow. Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent. To analyse the effects of treating anaesthesia-induced hypotension with noradrenaline on brain development of rabbit foetuses of mothers subjected to general anaesthesia for nonobstetric surgery. We hypothesised that treatment of maternal hypotension would improve foetal outcomes. Randomised controlled laboratory study using 21 pregnant rabbits (does) at 28 days of gestation. Two hours of sevoflurane anaesthesia for a laparotomy without treatment of anaesthesia-induced hypotension (hypotension group) or with maintaining maternal mean arterial pressure above 80% of the awake value using noradrenaline (noradrenaline group). In the control group, does remained untouched. At term, all pups were delivered by caesarean section. One day later, the neurobehaviour of the pups was assessed and brains were harvested. Neuron density in the frontal cortex for the comparison of noradrenaline groups versus hypotension groups was the primary outcome; the neurobehavioural scores and other histological outcomes were secondary outcomes. In the noradrenaline groups and hypotension groups, neuron density in the frontal cortex was similar (1181 ±â€Š162 versus 1189 ±â€Š200 neurons mm-2, P  = 0.870). However, significantly less foetal survival, lower sensory scores in neurobehavioural assessment and less proliferation were observed in the noradrenaline group when compared with the hypotension group. Neuron densities in other regions, total cell densities, biometrics and synaptogenesis were not affected. There were no differences between the control group and hypotension group. During general anaesthesia for nonobstetric surgery in rabbits, treatment of anaesthesia-induced hypotension using noradrenaline did not affect neuron densities but was associated with impaired foetal outcomes according to several secondary outcome parameters. Further studies are needed to investigate any clinical relevance and to determine the target blood pressure in pregnant women during general anaesthesia.KEY POINTSIn pregnant women, anaesthesia-induced hypotension is commonly treated using phenylephrine or noradrenaline, with the rationale to maintain uterine perfusion pressure and thereby uterine blood flow.Evidence for this strategy during general anaesthesia for nonobstetric surgery is absent.We investigated the effects of treating anaesthesia-induced hypotension with noradrenaline on the brain development of rabbit foetuses, of mothers subjected to general anaesthesia for nonobstetric surgery.We hypothesised that treatment of maternal hypotension would improve foetal outcomes.Neuron densities were similar but significantly less foetal survival, impaired neurobehaviour and less proliferation were observed after treatment of anaesthesia-induced hypotension with noradrenaline, compared with untreated hypotension.

Control of Postoperative Hypotension Using a Closed-Loop System for Norepinephrine Infusion in Patients After Cardiac Surgery: A Randomized Trial.

BACKGROUND: Vasopressors are a cornerstone for the management of vasodilatory hypotension. Vasopressor infusions are currently adjusted manually to achieve a predefined arterial pressure target. We have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently during the perioperative period. We tested the hypothesis that patients managed using such a system postcardiac surgery would present less hypotension compared to patients receiving standard management. METHODS: A total of 40 patients admitted to the intensive care unit (ICU) after cardiac surgery were randomized into 2 groups for a 2-hour study period. In all patients, the objective was to maintain mean arterial pressure (MAP) between 65 and 75 mm Hg using norepinephrine. In the CLV group, the norepinephrine infusion was controlled via the CLV system; in the control group, it was adjusted manually by the ICU nurse. Fluid administration was standardized in both groups using an assisted fluid management system linked to an advanced hemodynamic monitoring system. The primary outcome was the percentage of time patients were hypotensive, defined as MAP <65 mm Hg, during the study period. RESULTS: Over the 2-hour study period, the percentage of time with hypotension was significantly lower in the CLV group than that in the control group (1.4% [0.9-2.3] vs 12.5% [9.9-24.3]; location difference, -9.8% [95% CI, -5.4 to -15.9]; P < .001). The percentage of time with MAP between 65 and 75 mm Hg was also greater in the CLV group (95% [89-96] vs 66% [59-77]; location difference, 27.6% [95% CI, 34.3-19.0]; P < .001). The percentage of time with an MAP >75 mm Hg (and norepinephrine still being infused) was also significantly lower in patients in the CLV group than that in the control group (3.2% [1.9-5.4] vs 20.6% [8.9-32.5]; location difference, -17% [95% CI, -10 to -24]; P < .001).The number of norepinephrine infusion rate modifications over the study period was greater in the CLV group than that in the control group (581 [548-597] vs 13 [11-14]; location difference, 568 [578-538]; P < .001). No adverse event occurred during the study period in both groups. CONCLUSIONS: Closed-loop control of norepinephrine infusion significantly decreases postoperative hypotension compared to manual control in patients admitted to the ICU after cardiac surgery.

Norepinephrine pressor infusion withdrawal in a National Health Service hospice.

Norepinephrine (NE) is a peripheral vasoconstrictor used as an emergency measure to restore blood pressure secondary to acute hypotension. NE must be administered centrally as a continuous infusion and requires intensive monitoring. Consequently, its use is restricted to critical care environments. We discuss the withdrawal of NE in a hospice for a patient with advanced malignancy and profound hypotension from sepsis. The patient was admitted to intensive care but chose to stop active treatment and insisted on being discharged. Due to concerns about withdrawing NE in the community, he was transferred to a local hospice. We describe various challenges, including the administration and monitoring of NE outside of intensive care, the withdrawal process and concerns that profound hypotension might compromise subcutaneous medications absorption.

Hemodynamic effects of norepinephrine versus phenylephrine infusion for prophylaxis against spinal anesthesia-induced hypotension in the elderly population undergoing hip fracture surgery: a randomized controlled trial.

BACKGROUND: Elderly population are at increased risk of spinal anesthesia-induced hypotension increasing their risk for postoperative morbidity and mortality. This study aimed to compare the hemodynamic effects of prophylactic infusion of norepinephrine (NE) versus phenylephrine (PE) in elderly patients undergoing hip fracture surgery under spinal anesthesia. METHODS: Elderly patients scheduled for hip fracture surgery were randomized to receive either NE infusion (8 µg/min) (NE group, n = 31) or PE infusion (100 µg/min) (PE group, n = 31) after spinal anesthesia. Outcomes included mean heart rate, mean blood pressure, cardiac output, incidence of spinal anesthesia-induced hypotension, incidence of bradycardia, and incidence of hypertension. RESULTS: Sixty-two patients with a mean age of 71 ± 6 years were included in the final analysis (31 patients in each group). The NE group showed a higher mean heart rate and cardiac output than the PE group. The NE group had a lower incidence of reactive bradycardia (10% vs. 36%, P = 0.031) and hypertension (3% vs. 36%, P = 0.003) than the PE group. No study participant developed hypotension, and the mean blood pressure was comparable between the two groups. CONCLUSIONS: Both NE and PE infusions effectively prevented spinal anesthesia-induced hypotension in elderly patients undergoing hip fracture surgery. However, NE provided more hemodynamic stability than PE; maintaining the heart rate, higher cardiac output, less reactive bradycardia, and hypertension.

Clinical features, complications, and outcomes of exogenous and endogenous catecholamine-triggered Takotsubo syndrome: A systematic review and meta-analysis of 156 published cases.

Innumerable physical stress factors including externally administered catecholamines, and pheochromocytomas and paragangliomas (PPGLs) have been reported to trigger Takotsubo syndrome (TS). A systematic search of PubMed/MEDLINE identified 156 patients with catecholamine-induced TS up to December 2017. Data were compared within the catecholamine-induced TS cohort, but some comparisons were also done to a previously published large all-TS cohort (n = 1750). The mean age was 46.4 ± 16.4 years (72.3% women). The clinical presentation was dramatic with high complication rates in (68.2%, n = 103; multiple complications 34.6%, n = 54). The most common TS ballooning pattern was apical or mid-apical (45.2%, n = 69), followed by basal pattern (28.8%, n = 45), global pattern (16.0%, n = 25), mid-ventricular (8.3%, n = 13), focal (0.6%, n = 1), and unidentified pattern (1.9%, n = 3). There was an increase in the prevalence of apical sparing ballooning pattern compared to all-TS population (37.7% vs 18.3%, P < .00001). Higher complication rates were observed in TS with global ballooning pattern compared to apical ballooning pattern (23/25, 92% vs 38/65, 58.5%; P = .0022). Higher complication rates were observed in patients with age < 50 years than patients >50 years (73/92, 79.3% vs 29/56, 51.8%, P = 0.0009). Recurrence occurred exclusively in patients with PPGL-induced TS (18/107 patients, 16.8%). PPGL-induced TS was characterized by more global ballooning's pattern (22/104, 21.2% vs 3/49, 6.1%, P = 0.02), and lower left ventricular ejection fraction (25.54 ± 11.3 vs 31.82 ± 9.93, P = 0.0072) compared to exogenous catecholamine-induced TS. In conclusion, catecholamine-induced TS was characterized by a dramatic clinical presentation with extensive left ventricular dysfunction, and high complication rate.

Efficacy and Safety of Vasopressin as First-Line Treatment of Distributive and Hemorrhagic Shock States.

Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.

Norepinephrine-associated left ventricular outflow tract obstruction and systolic anterior movement.

In the perioperative setting, norepinephrine is used to increase blood pressure, an effect mediated mostly via arterial and venous vasoconstriction. Thus, norepinephrine is, allegedly, less likely to cause or worsen left ventricular outflow tract obstruction (LVOTO) than other inotropes. We report a case of norepinephrine-associated dynamic LVOTO and systolic anterior movement in a predisposed patient. This report highlights that unrecognised dynamic LVOTO may worsen shock parameters in patients treated with norepinephrine who have underlying myocardial hypertrophy.

Eventos adversos durante transporte intra-hospitalar de pacientes críticos em hospital de grande porte / Adverse events during intrahospital transport of critically ill patients in a large hospital

RESUMO Objetivo: Descrever a incidência de eventos clínicos e não clínicos durante o transporte intra-hospitalar de pacientes críticos e analisar os fatores de risco associados. Métodos: Estudo de coorte, com coleta retrospectiva, no período de outubro de 2016 a outubro de 2017, tendo sido analisados todos os transportes intra-hospitalares para fins diagnósticos e terapêuticos em hospital de grande porte, que contava com seis unidades de terapia intensiva adulto, sendo avaliados os eventos adversos e os fatores de risco relacionados. Resultados: No período, foram realizados 1.559 transportes intra-hospitalares, em 1.348 pacientes, com média de idade de 66 ± 17 anos, tempo médio de transporte de 43 ± 34 minutos. Durante o transporte, 19,8% dos pacientes estavam em uso de drogas vasoativas; 13,7% em uso de sedativos e 10,6% estavam sob ventilação mecânica. Eventos clínicos ocorreram em 117 transportes (7,5%) e não clínicos em 125 transportes (8,0%). Falhas de comunicação foram prevalentes, no entanto, aplicando-se análise multivariada, uso de sedativos, noradrenalina e nitroprussiato, e o tempo de transporte maior que 36,5 minutos estiveram associados a eventos adversos clínicos. Uso de dobutamina e tempo de transporte superior a 36,5 minutos estiveram associados a eventos não clínicos. Ao final do transporte, 98,1% dos pacientes apresentaram condições clínicas inalteradas em relação ao seu estado basal. Conclusão: Transportes intra-hospitalares estão relacionados à alta incidência de eventos adversos; o tempo de transporte e a utilização de sedativos e drogas vasoativas estiveram relacionados a esses eventos.

ABSTRACT Objective: To describe the incidence of clinical and non-clinical events during intrahospital transport of critically ill patients and to analyze the associated risk factors. Methods: Cohort study with retrospective data collected from October 2016 to October 2017. All cases of intrahospital transport for diagnostic and therapeutic purposes in a large hospital with six adult intensive care units were analyzed, and the adverse events and related risk factors were evaluated. Results: During the study period, 1,559 intrahospital transports were performed with 1,348 patients, with a mean age of 66 ± 17 years and a mean transport time of 43 ± 34 minutes. During transport, 19.8% of the patients were using vasoactive drugs; 13.7% were under sedation; and 10.6% were under mechanical ventilation. Clinical events occurred in 117 transports (7.5%), and non-clinical events occurred in 125 (8.0%) transports. Communication failures were prevalent; however, the multivariate analysis showed that the use of sedatives, noradrenaline and nitroprusside and a transport time greater than 36.5 minutes were associated with adverse clinical events. The use of dobutamine and a transport time greater than 36.5 minutes were associated with non-clinical events. At the end of transport, 98.1% of the patients presented unchanged clinical conditions compared with baseline. Conclusion: Intrahospital transport is related to a high incidence of adverse events, and transport time and the use of sedatives and vasoactive drugs were related to these events.

Intraoperative infusion of noradrenaline improves platelet aggregation in patients undergoing coronary artery bypass grafting: a randomized controlled trial.

Essentials Strategies to improve platelet function may reduce excessive bleeding during cardiac surgery. Patients were randomized to standard care or standard care + noradrenaline infusion. Low-dose noradrenaline improved intraoperative platelet aggregation and clot formation. Noradrenaline may be considered to improve intraoperative hemostasis during cardiac surgery. SUMMARY: Background New approaches to prevent bleeding complications during cardiac surgery are needed. Objective To investigate if noradrenaline (NA) enhances platelet aggregation in patients undergoing coronary artery bypass grafting (CABG). Patients/Methods Twenty-four patients undergoing coronary artery bypass grafting (CABG) were included in a prospective parallel-group randomized study. All patients but one were treated with acetylsalicylic acid (ASA). In the treatment group (n = 12), mean arterial blood pressure (MAP) was maintained at pre-induction levels by NA infusion. In the control group (n = 12), NA was administered only if MAP decreased below 60 mmHg. Platelet aggregation (impedance aggregometry with ADP, arachidonic acid [AA] and thrombin-receptor activating peptide [TRAP] as initiators) and clot formation (clotting time, clot formation time and maximum clot firmness by EXTEM, INTEM and FIBTEM tests with thromboelastometry) were assessed before and 50 min after anesthesia induction (before cardiopulmonary bypass was initiated). Results All patients in the treatment group received NA (median dose after 50 min 0.09 (range 0-0.26) µg kg-1  min-1 ). Four patients in the control group also received NA (0.03-0.12 µg kg-1  min-1 ). There were differences between the treatment group and the control group in ADP- and AA-induced aggregation changes (ADP, +16 [25th-75th percentiles, 5-26] vs. -7 [-19 to -1] U; AA, +12 [-4 to 16] vs. -9 [-13 to 1] U). INTEM maximum clot firmness increased in the treatment group but not in the control group. Conclusion Infusion of clinically relevant doses of NA enhanced platelet aggregation and clot firmness in ASA-treated CABG patients. NA infusion is hence a potential new method to acutely improve platelet reactivity in patients on antiplatelet therapy undergoing surgery.

Surgical treatment of extravasation injuries: experience of the Hospital das Clínicas, Faculty of Medicine, University of São Paulo. / Opções de tratamento cirúrgico em lesões cutâneas por extravasamento acidental de drogas: experiência do Hospital das Clínicas da Faculdade de Medicina da USP.

OBJECTIVE: to report the experience of the Division of Plastic Surgery of the Hospital das Clínicas of the Medical School of the University of São Paulo in the treatment of cutaneous lesions due to accidental extravasation of drugs. METHODS: we included patients with lesions due to extravasation of drugs over a period of 18 months. We retrospectively evaluated the following parameters: age, diagnoses during hospitalization and comorbidities, serum levels of albumin and hemoglobin, place of hospitalization, drug involved, anatomic segment affected, therapeutic management and death during hospitalization. RESULTS: we followed-up 14 patients. The main drug involved was noradrenaline (21%). All patients underwent debridement of tissue necrosis. Three patients were submitted to flaps after preparation of the wound bed with negative pressure therapy, with good results. Seven patients had no definitive treatment of their lesions due to lack of clinical conditions. CONCLUSION: in patients with favorable clinical conditions, the definitive treatment with flaps was adequate for cases of wounds due to extravasation of drugs in the subcutaneous tissue when there was exposure of noble structures.

OBJETIVO: relatar a experiência da Divisão de Cirurgia Plástica do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo no tratamento de lesões cutâneas por extravasamento acidental de drogas. MÉTODOS: foram incluídos os pacientes com lesões por extravasamento de drogas num período de 18 meses. Os seguintes parâmetros foram avaliados retrospectivamente: idade, diagnósticos durante internação e comorbidades, níveis séricos de albumina e hemoglobina, local de internação, droga envolvida, segmento anatômico acometido, conduta terapêutica e óbito durante internação. RESULTADOS: foram acompanhados 14 pacientes. A principal droga envolvida foi a noradrenalina (21%). Todos os pacientes foram submetidos a desbridamento da necrose tecidual. Três pacientes foram submetidos a retalhos após preparo do leito com terapia por pressão negativa, com bons resultados. Sete pacientes não tiveram tratamento definitivo de suas lesões por falta de condições clínicas. CONCLUSÃO: o tratamento definitivo por meio de retalhos se mostrou adequado para os casos de feridas por extravasamento de drogas em tecido subcutâneo, quando há exposição de estruturas nobres, em pacientes com condições clínicas favoráveis.

Impact of intra-operative fluid and noradrenaline administration on early postoperative renal function after cystectomy and urinary diversion: A retrospective observational cohort study.

BACKGROUND: The use of noradrenaline to enable a restrictive approach to intra-operative fluid therapy to avoid salt and water overload has gained increasing acceptance. However, concerns have been raised about the impact of this approach on renal function. OBJECTIVES: To identify risk factors for acute kidney injury (AKI) in patients undergoing cystectomy with urinary diversion and determine whether administration of noradrenaline and intra-operative hydration regimens affect early postoperative renal function. DESIGN: Retrospective observational cohort study. SETTING: University hospital, from 2007 to 2016. PATIENTS: A total of 769 consecutive patients scheduled for cystectomy and urinary diversion. Those with incomplete data and having pre-operative haemodialysis were excluded. MAIN OUTCOME MEASURES: AKI was defined as a serum creatinine increase of more than 50% over 72 postoperative hours. Multiple logistic regression analysis was performed to model the association between risk factors and AKI. RESULTS: Postoperative AKI was diagnosed in 86/769 patients (11.1%). Independent predictors for AKI were the amount of crystalloid administered (odds ratio (OR) 0.79 [95% confidence interval (CI), 0.68 to 0.91], P = 0.002), antihypertensive medication (OR 2.07 [95% CI, 1.25 to 3.43], P = 0.005), pre-operative haemoglobin value (OR 1.02 [95% CI, 1.01 to 1.03], P = 0.010), duration of surgery (OR 1.01 [95% CI, 1.00 to 1.01], P = 0.002), age (OR 1.32 [95% CI, 1.44 to 1.79], P = 0.002) but not the administration of noradrenaline (OR 1.09 [95% CI, 0.94 to 1.21], P = 0.097). Postoperative AKI was associated with longer hospital stay (18 [15 to 22] vs. 16 [15 to 19] days; P = 0.035) and a higher 90-day major postoperative complication rate (41.9 vs. 27.5%; P = 0.002). CONCLUSION: Noradrenaline administration did not increase the risk for AKI. A too restrictive approach to administration of crystalloids was associated with an increased risk for AKI, particularly in older patients, those receiving antihypertensive medication, and those whose surgery was prolonged. As AKI was associated with longer hospital stay and increased postoperative morbidity, these observations should be taken into account to improve outcome when addressing peri-operative fluid management. TRIAL REGISTRATION: Not applicable.

High-Target Versus Low-Target Blood Pressure Management During Cardiopulmonary Bypass to Prevent Cerebral Injury in Cardiac Surgery Patients: A Randomized Controlled Trial.

BACKGROUND: Cerebral injury is an important complication after cardiac surgery with the use of cardiopulmonary bypass. The rate of overt stroke after cardiac surgery is 1% to 2%, whereas silent strokes, detected by diffusion-weighted magnetic resonance imaging, are found in up to 50% of patients. It is unclear whether a higher versus a lower blood pressure during cardiopulmonary bypass reduces cerebral infarction in these patients. METHODS: In a patient- and assessor-blinded randomized trial, we allocated patients to a higher (70-80 mm Hg) or lower (40-50 mm Hg) target for mean arterial pressure by the titration of norepinephrine during cardiopulmonary bypass. Pump flow was fixed at 2.4 L·min-1·m-2. The primary outcome was the total volume of new ischemic cerebral lesions (summed in millimeters cubed), expressed as the difference between diffusion-weighted imaging conducted preoperatively and again postoperatively between days 3 and 6. Secondary outcomes included diffusion-weighted imaging-evaluated total number of new ischemic lesions. RESULTS: Among the 197 enrolled patients, mean (SD) age was 65.0 (10.7) years in the low-target group (n=99) and 69.4 (8.9) years in the high-target group (n=98). Procedural risk scores were comparable between groups. Overall, diffusion-weighted imaging revealed new cerebral lesions in 52.8% of patients in the low-target group versus 55.7% in the high-target group (P=0.76). The primary outcome of volume of new cerebral lesions was comparable between groups, 25 mm3 (interquartile range, 0-118 mm3; range, 0-25 261 mm3) in the low-target group versus 29 mm3 (interquartile range, 0-143 mm3; range, 0-22 116 mm3) in the high-target group (median difference estimate, 0; 95% confidence interval, -25 to 0.028; P=0.99), as was the secondary outcome of number of new lesions (1 [interquartile range, 0-2; range, 0-24] versus 1 [interquartile range, 0-2; range, 0-29] respectively; median difference estimate, 0; 95% confidence interval, 0-0; P=0.71). No significant difference was observed in frequency of severe adverse events. CONCLUSIONS: Among patients undergoing on-pump cardiac surgery, targeting a higher versus a lower mean arterial pressure during cardiopulmonary bypass did not seem to affect the volume or number of new cerebral infarcts. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02185885.

Role of the ß3-adrenergic receptor subtype in catecholamine-induced myocardial remodeling.

ß3-Adrenoceptors (AR) stimulate cardiac Na+/K+ pump in healthy hearts. ß3-ARs are upregulated by persistent sympathetic hyperactivity; however, their effect on Na+/K+ ATPase activity and ventricular function in this condition is still unknown. Here, we investigate preventive effects of additional ß3-AR activation (BRL) on Na+/K+ ATPase activity and in vivo hemodynamics in a model of noradrenaline-induced hypertrophy. Rats received NA or NA plus simultaneously administered BRL in vivo infusion for 14 days; their cardiac function was investigated by left ventricular pressure-volume analysis. Moreover, fibrosis and apoptosis were also assessed histologically. NA induced an hypertrophic pattern, as detected by morphological, histological, and biochemical markers. Additional BRL exposure reversed the hypertrophic pattern and restored Na+/K+ ATPase activity. NA treatment increased systolic function and depressed diastolic function (slowed relaxation). Additional BRL treatment reversed most NA-induced hemodynamic changes. NA decreased Na+/K+ pump α2 subunit expression selectively, a change also reversed by additional BRL treatment. Increasing ß3-AR stimulation may prevent the consequences of chronic NA exposure on Na+/K+ pump and in vivo hemodynamics. ß3-AR agonism may thus represent a new therapeutic strategy for pharmacological modulation of hypertrophy under conditions of chronically enhanced sympathetic activity.

The Disparate Effects of Epinephrine and Norepinephrine on Hyperglycemia in Cardiovascular Surgery.

Hyperglycemia is a metabolic derangement that frequently develops after cardiovascular surgery. The perioperative administration of inotropic and vasoactive agents, such as epinephrine and norepinephrine, are common in the management of cardiac surgery patients and are known to contribute to the development of postoperative hyperglycemia. We hypothesized that hemodynamic support with epinephrine exacerbates postoperative hyperglycemia to a greater degree than does treatment with norepinephrine. This literature review outlines the mechanisms by which epinephrine and norepinephrine alter glucose homeostasis, while highlighting the significant differences in their effects on hepatic glucose mobilization and peripheral glucose utilization. This review suggests that the use of epinephrine exacerbates postoperative hyperglycemia to a greater degree than does norepinephrine.