Effects and mechanisms of perioperative medications on the hypothalamic pituitary adrenal response to surgical injury: A narrative review.

The adrenal gland is a vital endocrine organ, and adrenal steroid synthesis and secretion are closely regulated by the hypothalamic-pituitary-adrenal (HPA) axis in response to various stimuli. Surgery or trauma can activate the HPA axis and induce the secretion of cortisol. Different cortisol responses vary with the grade of surgery. Perioperative medications have the potential to decrease the cortisol level in the body, and both excessive and insufficient cortisol levels after surgery are disadvantageous. The effect of perioperative medications on the HPA response to surgery can be divided into three levels: "adrenal insufficiency (AI)", "stress response inhibition", and "uncertainty". The clinical presentation of AI includes fatigue, nausea, vomiting, abdominal pain, muscle cramps, hypotension, hypovolemic shock and prerenal failure, which may result in fatal consequences. Stress response inhibition can reduce postoperative complications, such as pain and cognitive dysfunction. This is protective to patients during perioperative and postoperative periods. The aim of the present review is to shed light on current evidence regarding the exact effects and mechanisms of perioperative medications on the HPA response to surgical injury and provide the applicable guidance on clinical anesthesia.

Risk factors for intraoperative complications in pheochromocytomas.

We aimed to identify presurgical and surgical risk factors for intraoperative complications in patients with pheochromocytomas. A retrospective study of patients with pheochromocytomas who underwent surgery in ten Spanish hospitals between 2011 and 2021 was performed. One hundred and sixty-two surgeries performed in 159 patients were included. The mean age was 51.6 ± 16.4 years old and 52.8% were women. Median tumour size was 40 mm (range 10-110). Laparoscopic adrenalectomy was performed in 148 patients and open adrenalectomy in 14 patients. Presurgical alpha- and beta-blockade was performed in 95.1% and 51.9% of the surgeries, respectively. 33.3% of the patients (n = 54) had one or more intraoperative complications. The most common complication was the hypertensive crisis in 21.0%, followed by prolonged hypotension in 20.0%, and hemodynamic instability in 10.5%. Patients pre-treated with doxazosin required intraoperative hypotensive treatment more commonly than patients pre-treated with other antihypertensive drugs (51.1% vs 26.5%, P = 0.002). Intraoperative complications were more common in patients with higher levels of urine metanephrine (OR = 1.01 for each 100 µg/24 h, P = 0.026) and normetanephrine (OR = 1.00 for each 100 µg/24 h, P = 0.025), larger tumours (OR = 1.4 for each 10 mm, P < 0.001), presurgical blood pressure > 130/80 mmHg (OR = 2.25, P = 0.027), pre-treated with doxazosin (OR = 2.20, P = 0.023) and who had not received perioperative hydrocortisone (OR = 3.95, P = 0.008). In conclusion, intraoperative complications in pheochromocytoma surgery are common and can be potentially life-threatening. Higher metanephrine and normetanephrine levels, larger tumour size, insufficient blood pressure control before surgery, pre-treatment with doxazosin, and the lack of treatment with perioperative hydrocortisone are associated with higher risk of intraoperative complications.

Transplantation of Pluripotent Stem Cell-Derived Cardiomyocytes into a Myocardial Infarction Model of Cynomolgus Monkey.

Recent evidence has provided exciting proof of concepts for the use of pluripotent stem cell-derived cardiomyocytes (PSC-CMs) for cardiac repair; however, large animal studies, which better reflect human disease, are required for clinical application. Here, we describe how to create myocardial infarction in cynomolgus monkey followed by transplantation of PSC-CMs. This method ensures the establishment of a myocardial infarction model and enables reliable PSC-CM transplantation.

Successful rescue treatment of right posterior inferior cerebellar artery (PICA) vascular stasis with tirofiban following endovascular coil implantation.

This report describes a patient who developed intraprocedural vascular stasis immediately following elective endovascular coil emboliation. Urgent antiplatelet treatment with the GpIIb/IIIa agent tirofiban was used. It was infused intra-arterially during the procedure, followed by a fixed rate intravenous continuous infusion, and successfully restored normal circulation. There were no reports of further bleeding or haemodynamic compromise during the hospital stay. The patient's condition returned to baseline and he was discharged the following day with no neurological deficits.

Automated closed-loop versus manually controlled norepinephrine infusion in patients undergoing intermediate- to high-risk abdominal surgery: a randomised controlled trial.

BACKGROUND: Hypotension occurs frequently during surgery and may be associated with adverse complications. Vasopressor titration is frequently used to correct hypotension, but requires considerable time and attention, potentially reducing the time available for other clinical duties. To overcome this issue, we have developed a closed-loop vasopressor (CLV) controller to help correct hypotension more efficiently. The aim of this randomised controlled study was to evaluate whether the CLV controller was superior to traditional vasopressor management at minimising hypotension in patients undergoing abdominal surgery. METHODS: Thirty patients scheduled for elective intermediate-to high-risk abdominal surgery were randomised into two groups. In the CLV group, hypotension was corrected automatically via the CLV controller system, which adjusted the rate of a norepinephrine infusion according to MAP values recorded using an advanced haemodynamic device. In the control group, management of hypotension consisted of standard, manual adjustment of the norepinephrine infusion. The primary outcome was the percentage of time that a patient was hypotensive, defined as MAP <90% of their baseline value, during surgery. RESULTS: The percentage of time patients were hypotensive during surgery was 10 times less in the CVL group than in the control group (1.6 [0.9-2.3]% vs 15.4 [9.9-24.3]%; difference: 13 [95% confidence interval: 9-19]; P<0.0001). The CVL group also spent much less time with MAP <65 mm Hg (0.2 [0.0-0.4]% vs 4.5 [1.1-7.9]%; P<0.0001). CONCLUSIONS: In patients undergoing intermediate- to high-risk surgery under general anaesthesia, computer-assisted adjustment of norepinephrine infusion significantly decreases the incidence of hypotension compared with manual control. CLINICAL TRIAL REGISTRATION: NCT04089644.

A simple procedure in a complex patient: perioperative takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TTC) is a rare but life-threatening condition that is still not completely understood. Characterised by rapidly reversible ventricular dysfunction without any prior coronary artery disease, it can imitate a myocardial infarction and lead to death if not managed appropriately. This report examines a case of intraoperative cardiac arrest in a patient with no previous cardiac disease, and discusses the factors that may have precipitated this event, as well as the ways of distinguishing the cause of the arrest based on clinical course and investigations, eventually leading to a diagnosis of TTC.

Retrospective evaluation of labetalol as antihypertensive agent in dogs.

BACKGROUND: To evaluate the effect on arterial blood pressure (ABP) of labetalol infusion as treatment for perioperative non nociceptive acute hypertension in dogs. The clinical records of dogs receiving intra or postoperative labetalol infusion were retrospectively reviewed. Invasive systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressure and heart rate (HR) before labetalol infusion (T0) and 15, 30, 45 and 60 min (T1, T2, T3 and T4 respectively) after infusion were retrieved. The dose rate of labetalol infusion and use of concurrently administered drugs that could have potentially affected ABP and/or HR were also recorded. ANOVA for repeated measures and Dunnett's multiple comparison test were used to determine the effect of labetalol on ABP and HR. Differences were considered significant when p < 0.05. RESULTS: A total of 20 dogs met the inclusion criteria, and hypertension was documented after craniotomy (12/20), adrenalectomy (4/20) and other procedures (4/20). Five dogs received labetalol intraoperatively, 14 postoperatively, and 1 during the surgical procedure and recovery. Median infusion duration and rate were 463 (60-2120) minutes and 1.1 (0.2-3.4) mg/kg/h respectively. Median loading dose was 0.2 (0.2-0.4) mg/kg. Labetalol produced a significant decrease in SAP and DAP at all time points compared to T0 (p < 0.05), while the effect was not significant at T1 for MAP (p = 0.0519). Median maximum MAP decrease was 31 (20-90) mmHg. Heart rate did not increase significantly during treatment (p = 0.2454). Acepromazine given before or during labetalol treatment did not reduce significantly ABP (p = 0.735). CONCLUSIONS: Labetalol produced a reliable and titratable decrease in ABP with non significant increase in HR.

Does topical application of tranexamic acid reduce intraoperative bleeding in sinus surgery during general anesthesia? / A aplicação tópica de ácido tranexâmico reduz o sangramento intraoperatório em cirurgia sinusal durante anestesia geral?

Abstract Introduction Tranexamic acid is a hemostatic agent, which inhibits fibrin degradation, which may be beneficial in controlling bleeding during surgery. Objectives The purpose of this study was to provide a meta-analysis and review of the effects of tranexamic acid on hemorrhage and surgical fields and side effects on patients during endoscopic sinus surgery. Methods Two authors independently searched six databases (Medline, Scopus, Embase, Web of Science, Google Scholar and Cochrane library) from the start of article collection until July 2018. Postoperative complications such as intraoperative bleeding, operative time, hypotension, nausea, vomiting, and coagulation profile were included in the analysis of tranexamic acid (Treatment Group) and placebo (Control Group) during the operation. Results The amount of blood loss during surgery was statistically lower in the treatment group compared to the placebo group, and the surgical field quality was statistically higher in the treatment group than in the placebo group. On the other hand, there was no significant difference in operation time, hemodynamics, or coagulation profile between groups. In addition, tranexamic acid had no significant effect on vomiting and thrombosis compared to the Control Group. Conclusion This meta-analysis has shown that topical administration of tranexamic acid can reduce the amount of bleeding during surgery and improve the overall quality of the surgery. Hemodynamic instability during surgery, vomiting after surgery, or abnormal clotting profile were not reported. Additional studies are needed to confirm the results of this study because there are fewer studies.

Resumo Introdução O ácido tranexâmico é um agente hemostático, que inibe a degradação da fibrina e pode ser benéfico no controle do sangramento durante a cirurgia. Objetivos Fazer uma metanálise e revisão dos efeitos do ácido tranexâmico na hemorragia e nos campos cirúrgicos e efeitos colaterais em pacientes durante a cirurgia endoscópica do seio nasal. Método Dois autores realizaram independentemente uma busca em seis bancos de dados (Medline, Scopus, Embase, Web of Science, Google Scholar e Cochrane) desde o início da coleta de artigos até julho de 2018. Complicações pós-operatórias como sangramento intraoperatório, tempo operatório, hipotensão, náusea, vômitos e perfil de coagulação foram incluídos na análise do ácido tranexâmico (grupo de tratamento) e placebo (grupo controle) durante a cirurgia. Resultados A quantidade de perda de sangue durante a cirurgia foi estatisticamente menor no grupo de tratamento comparado com o grupo placebo e a qualidade do campo cirúrgico foi estatisticamente maior no grupo de tratamento do que no grupo placebo. Por outro lado, não houve diferença significante no tempo cirúrgico, hemodinâmica ou perfil de coagulação entre os grupos. Além disso, o ácido tranexâmico não teve efeito significante na ocorrência de vômitos e trombose em comparação ao grupo controle. Conclusão Esta metanálise mostrou que a administração tópica de ácido tranexâmico pode reduzir a quantidade de sangramento durante a cirurgia e melhorar a qualidade geral dela. Instabilidade hemodinâmica durante a cirurgia, vômitos após a cirurgia ou perfil de coagulação anormal não foram relatados. Estudos adicionais são necessários para confirmar os resultados desta pesquisa, porque há poucos estudos na literatura.

Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation.

Increased concentrations of the vasodilator histamine have been observed in patients undergoing abdominal surgery. The role of histamine during orthotopic liver transplantation (OLT) has only been studied in animals. The aim of this study was to measure plasma concentrations of histamine and its degrading enzyme diamine oxidase (DAO) in patients undergoing orthotopic liver transplantation, and assess whether histamine or DAO correlate with intraoperative noradrenaline requirements. Histamine and DAO concentrations were measured in 22 adults undergoing liver transplantation and 22 healthy adults. Furthermore, norepinephrine requirements during liver transplantation were recorded. Baseline concentrations of histamine and DAO were greater in patients, who underwent liver transplantation, than in healthy individuals (Histamine: 6.4 nM, IQR[2.9-11.7] versus 4.3 nM, IQR[3.7-7.1], p = 0.029; DAO: 2.0 ng/mL, IQR[1.5-4.1] versus <0,5 ng/mL, IQR[<0.5-1.1], p < 0.001). During liver transplantation, histamine concentrations decreased to 1.8 nM, IQR[0.5-4.9] in the anhepatic phase (p < 0.0001 versus baseline), and to 1.5 nM, IQR[0.5-2.9] after reperfusion (p < 0.0001 versus baseline). In contrast, DAO concentrations increased to 35.5 ng/ml, IQR[20-50] in the anhepatic phase (p = 0.001 versus baseline) and to 39.5 ng/ml, IQR[23-64] after reperfusion (p = 0.001 versus baseline), correlating inversely with histamine. Norepinephrine requirements during human liver transplantation correlated significantly with DAO concentrations in the anhepatic phase (r = 0.58, p = 0.011) and after reperfusion (r = 0.56; p = 0.022). In patients undergoing orthotopic liver transplantation, histamine concentrations decrease whereas DAO concentrations increase manifold. Diamine oxidase correlates with intraoperative norepinephrine requirements in patients undergoing OLT.

Does topical application of tranexamic acid reduce intraoperative bleeding in sinus surgery during general anesthesia?

INTRODUCTION: Tranexamic acid is a hemostatic agent, which inhibits fibrin degradation, which may be beneficial in controlling bleeding during surgery. OBJECTIVES: The purpose of this study was to provide a meta-analysis and review of the effects of tranexamic acid on hemorrhage and surgical fields and side effects on patients during endoscopic sinus surgery. METHODS: Two authors independently searched six databases (Medline, Scopus, Embase, Web of Science, Google Scholar and Cochrane library) from the start of article collection until July 2018. Postoperative complications such as intraoperative bleeding, operative time, hypotension, nausea, vomiting, and coagulation profile were included in the analysis of tranexamic acid (Treatment Group) and placebo (Control Group) during the operation. RESULTS: The amount of blood loss during surgery was statistically lower in the treatment group compared to the placebo group, and the surgical field quality was statistically higher in the treatment group than in the placebo group. On the other hand, there was no significant difference in operation time, hemodynamics, or coagulation profile between groups. In addition, tranexamic acid had no significant effect on vomiting and thrombosis compared to the Control Group. CONCLUSION: This meta-analysis has shown that topical administration of tranexamic acid can reduce the amount of bleeding during surgery and improve the overall quality of the surgery. Hemodynamic instability during surgery, vomiting after surgery, or abnormal clotting profile were not reported. Additional studies are needed to confirm the results of this study because there are fewer studies.

Sudden arrhythmia followed by bradycardia during sagittal split ramus osteotomy: trigeminocardiac reflex.

Trigeminocardiac reflex (TCR) is a brainstem reflex triggered by the stimulation of any branch of the fifth cranial nerve along its course, presenting as a reduction in heart rate and blood pressure. Oculocardiac reflex is a well-known subtype of TCR. In the case reported here, remarkable arrhythmia followed by bradycardia occurred suddenly in a healthy patient undergoing orthognathic surgery. The heart rhythm recovered when the surgical manipulation ceased, but bradycardia was reproduced when the surgery resumed. This case of TCR is unique in that remarkable arrhythmia first appeared and led to bradycardia; accordingly, intravenous lidocaine and an anticholinergic agent were administered simultaneously instead of anticholinergic agents alone, and were protective. Although TCR rarely occurs during orthognathic surgery, clinicians should be aware of its possibility and able to judge and manage it promptly.

Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis.

BACKGROUND: Dexmedetomidine (DEX) is a highly selective alpha2 adrenoceptor agonist with broad pharmacological effects, including sedation, analgesia, anxiolysis, and sympathetic tone inhibition. Here we report a systematic review and meta-analysis of its effects on stress, inflammation, and immunity in surgical patients during the perioperative period. METHODS: We searched MEDLINE, METSTR, Embase, and Web of Science for clinical studies or trials to analyse the effects of DEX on perioperative stress, inflammation, and immune function. RESULTS: Sixty-seven studies (including randomised controlled trials and eight cohort studies) with 4842 patients were assessed, of which 2454 patients were in DEX groups and 2388 patients were in control (without DEX) groups. DEX infusion during the perioperative period inhibited release of epinephrine, norepinephrine, and cortisol; decreased blood glucose, interleukin (IL)-6, tumour necrosis factor-α, and C-reactive protein; and increased interleukin-10 in surgical patients. In addition, the numbers of natural killer cells, B cells, and CD4+ T cells, and the ratios of CD4+:CD8+ and Th1:Th2 were significantly increased; CD8+ T-cells were decreased in the DEX group when compared with the control group. CONCLUSIONS: DEX, an anaesthesia adjuvant, can attenuate perioperative stress and inflammation, and protect the immune function of surgical patients, all of which may contribute to decreased postoperative complications and improved clinical outcomes.

Continuous EEG monitoring after brain tumor surgery.

BACKGROUND: Prolonged seizures generate cerebral hypoxia and increased intracranial pressure, resulting in an increased risk of neurological deterioration, increased long-term morbidity, and shorter survival. Seizures should be recognized early and treated promptly. The aim of the study was to investigate the occurrence of postoperative seizures in patients undergoing craniotomy for primary brain tumors and to determine if non-convulsive seizures could explain some of the postoperative neurological deterioration that may occur after surgery. METHODS: A single-center prospective study of 100 patients with suspected glioma. Participants were studied with EEG and video recording for at least 24 h after surgery. RESULTS: Seven patients (7%) displayed seizure activity on EEG recording within 24 h after surgery and another two patients (2%) developed late seizures. One of the patients with early seizures also developed late seizures. In five patients (5%), there were non-convulsive seizures. Four of these patients had a combination of clinically overt and non-convulsive seizures and in one patient, all seizures were non-convulsive. The non-convulsive seizures accounted for the majority of total seizure time in those patients. Non-convulsive seizures could not explain six cases of unexpected postoperative neurological deterioration. Postoperative ischemic lesions were more common in patients with early postoperative seizures. CONCLUSIONS: Early seizures, including non-convulsive, occurred in 7% of our patients. Within this group, non-convulsive seizure activity had longer durations than clinically overt seizures, but only 1% of patients had exclusively non-convulsive seizures. Seizures were not associated with unexpected neurological deterioration.

Vitamin B12 for the treatment of vasoplegia in cardiac surgery and liver transplantation: a narrative review of cases and potential biochemical mechanisms.

PURPOSE: Hydroxocobalamin, or vitamin B12 (V-B12), is frequently used to treat smoke inhalation and cyanide poisoning. Recent reports have also described its use to treat vasoplegia in cardiac surgery and liver transplantation. This narrative review discusses this "off-label" indication for V-B12, focusing on the potential biochemical mechanisms of its actions. SOURCE: PubMed, Cochrane, and Web of Science databases were searched for clinical reports on the use of V-B12 for vasoplegia in cardiac surgery and liver transplantation, with the biochemical mechanisms discussed being based on a survey of the related biochemistry literature. PRINCIPAL FINDINGS: Forty-four patients have been treated with V-B12 for vasoplegia in various isolated case reports and one series. Although 75% of patients have increased blood pressure in response to V-B12, there were some "non-responders". The true efficacy remains unknown because clinical trials have not been performed, and significant reporting bias likely exists. Plausible biochemical explanations exist for the potential beneficial effects of V-B12 in treating vasoplegia, including binding nitric oxide and other gasotransmitters. Additional research is required to clarify if and how these mechanisms are causally involved in effective clinical responders and non-responders. CONCLUSIONS: Although anecdotal reports utilizing V-B12 for vasoplegia are available, no higher-level evidence exists. Future work is necessary to further understand the dosing, timing, adverse events, and biochemical mechanisms of V-B12 compared with other therapies such as methylene blue.

Asystole in Orthognathic Surgery: A Case Report.

A previously healthy 26-year-old man presented for elective Le Fort I osteotomy, bilateral mandibular osteotomy, and genioplasty. During the intraoperative course, the patient developed sudden bradycardia and asystole on placement of a bite block. Asystole is an extremely rare consequence of the trigeminocardiac reflex, and awareness of this potentially life-threatening complication is pivotal in its management.

A Clinical Review of Common Medications Used in Emergency Dermatological Situations.

BACKGROUND: Medical emergencies can occur in any environment, including dermatologic and procedural surgical settings. There are many options available to dermatologic surgeons, which they should consider having easily accessible in the office in case an emergency arises. OBJECTIVE: To summarize the current understanding about major medications that should be on-hand during dermatological surgeries. To review their mechanism of action, examine their general use, and dermatological use during surgical emergencies. METHODS AND MATERIALS: A comprehensive review using PubMed was performed, searching for studies using these various medications in relation to cutaneous surgeries. RESULTS: Distinct items such as hyaluronidase, nitroglycerin paste, aspirin, injectable epinephrine, and defibrillators are potential options to address various emergencies and should be readily accessible to dermatologic surgeons. CONCLUSION: Dermatologic surgeons' knowledge of key medications and options to have in the office allow for a proper response in the event an emergency arises.

In-stent Massive Thrombi Formation During Primary Percutaneous Coronary Intervention in a Patient with Acute Myocardial Infarction Complicated with Essential Thrombocythemia.

A 61-year-old man with essential thrombocythemia (ET) presented with acute myocardial infarction (AMI) and underwent primary percutaneous coronary intervention. After stent deployment from the left main (LM) to the left anterior descending artery, intravascular ultrasound revealed thrombi formation in the whole stent. Two days later, optical frequency domain imaging confirmed stent malapposition and thrombi remaining in only the LM. The stent malapposition and ET might have contributed to this phenomenon. He underwent an additional stent expansion and aggressive anti-thrombotic regimen. AMI complicated with ET carries increased risks of in-stent thrombi formation and requires careful revascularization and aggressive pharmacotherapy.

Β-Adrenergic agonist administration is not associated with secondary carcinoid crisis in patients with carcinoid tumor.

BACKGROUND: Patients with carcinoid tumors are at risk for profound intraoperative hypotension known as carcinoid crisis, which catecholamines are traditionally believed to trigger. However, data supporting this are lacking. METHODS: Anesthesia records were retrospectively reviewed for carcinoid patients treated with vasopressors. Hemodynamics for those with crisis were compared between those who received ß-adrenergic agonists (B-AA) versus those who did not. RESULTS: Among 293 consecutive operations, 58 were marked by 161 crises. There was no significant difference in the incidence of paradoxical hypotension with B-AA compared to non-B-AA (p = 0.242). The maximum percent decrease in mean arterial pressure following drug administration was significantly greater in those patients treated with non-B-AA than with B-AA (31.6% vs. 12.5%, p < 0.0001). There were no differences in crisis duration (p = 0.257) or postoperative complication rate (p = 0.896). CONCLUSIONS: ß-Adrenergic agonist use was not associated with paradoxical hypotension, prolonged carcinoid crisis, or postoperative complications in patients with intraoperative carcinoid crisis.