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1.
Drug Res (Stuttg) ; 74(6): 290-295, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38968952

RESUMO

BACKGROUND: There have been reports of serious side effects of Remdesivir, including cardiovascular complications. The present study aimed to determine the adverse cardiovascular effects of Remdesivir and the factors affecting them in COVID-19 patients. METHODS: The patients were classified into two groups: those receiving Remdesivir without cardiac complications and those receiving Remdesivir with cardiovascular complications. After reviewing the patient's medical records, the relationship of some factors with the incidence of adverse cardiovascular effects was measured. RESULTS: Chi-square test showed that the distribution of complications in men was significantly higher than in women (P=0.001). The independent t-test revealed that the mean age in the group with complications was significantly higher than the group without complications (P=0.013). Fisher's exact test demonstrated a significant relationship between smoking and cardiovascular complications (P=0.05). According to the Mann-Whitney test, a significant difference was found in the mean changes of Bilirubin (P=0.02) and ALKP (P=0.01) before and after treatment in the groups with and without heart complications. CONCLUSION: Our findings indicated that most of the COVID-19 patients suffered from sinus bradycardia, and the distribution of complications was more pronounced in men than in women. The mean age in the group with complications was higher than the group without complications. Smoking was found to be associated with the occurrence of cardiovascular complications and the mean changes of Bilirubin and ALKP before and after treatment were significantly different in the groups with and without cardiovascular complications.


Assuntos
Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Humanos , Masculino , Alanina/análogos & derivados , Alanina/efeitos adversos , Alanina/uso terapêutico , Feminino , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/efeitos adversos , Monofosfato de Adenosina/uso terapêutico , Pessoa de Meia-Idade , Antivirais/efeitos adversos , Antivirais/uso terapêutico , Estudos de Casos e Controles , Idoso , COVID-19/complicações , Adulto , SARS-CoV-2 , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Fatores Sexuais , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Estudos Retrospectivos
2.
Ann Med ; 56(1): 2361843, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38830017

RESUMO

BACKGROUND: Literature on the safety of remdesivir in hospitalized COVID-19 patients with severe renal impairment is limited. We aimed to investigate the safety and effectiveness of remdesivir in this population. METHODS: We conducted a retrospective cohort study of adult hospitalized COVID-19 patients who received remdesivir between April 2022 and October 2022. Outcomes were compared between estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and ≥30 mL/min/1.73 m2 groups. The primary safety outcomes were acute kidney injury (AKI) and bradycardia, while the primary effectiveness outcomes included mortality in COVID-19-dedicated wards and hospital mortality. Secondary outcomes included laboratory changes, disease progression, and recovery time. RESULTS: A total of 1,343 patients were recruited, with 307 (22.9%) in the eGFR <30 group and 1,036 (77.1%) in the eGFR ≥30 group. Patients with an eGFR <30 had higher risks of AKI (adjusted hazard ratio [aHR] 2.92, 95% CI 1.93-4.44) and hospital mortality (aHR 1.47, 95% CI 1.06-2.05) but had comparable risks of bradycardia (aHR 1.15, 95% CI 0.85-1.56) and mortality in dedicated wards (aHR 1.43, 95% CI 0.90-2.28) than patients with an eGFR ≥30. Risk of disease progression was higher in the eGFR <30 group (adjusted odds ratio 1.62, 95% CI 1.16-2.26). No difference between the two groups in laboratory changes and recovery time. CONCLUSIONS: Hospitalized COVID-19 patients receiving remdesivir with severe renal impairment had an increased risk of AKI, hospital mortality, and COVID-19 disease progression compared to patients without severe renal impairment.


Assuntos
Injúria Renal Aguda , Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , Taxa de Filtração Glomerular , Mortalidade Hospitalar , Hospitalização , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , Alanina/uso terapêutico , Alanina/efeitos adversos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Monofosfato de Adenosina/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Antivirais/uso terapêutico , Antivirais/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/epidemiologia , Hospitalização/estatística & dados numéricos , COVID-19/complicações , COVID-19/mortalidade , Resultado do Tratamento , Insuficiência Renal/epidemiologia , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Adulto
3.
Pediatr Dermatol ; 41(4): 621-627, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38631683

RESUMO

BACKGROUND: Infantile hemangiomas are common vascular tumors in children. Propranolol has proven effective in treating infantile hemangiomas and while generally safe, has potential risk for more serious side effects of hypoglycemia, hypotension, bradycardia, bronchospasm, and cardiovascular or respiratory compromise. Current prescribing guidelines recommend initiating propranolol doses at 1 mg/kg/day, with up-titration to 2 mg/kg/day. This study aims to compare the incidence of adverse events in infants and children treated with propranolol initiated at 1 mg/kg/day versus being initiated directly at 2 mg/kg/day. METHODS: A retrospective cohort study was conducted using medical records of patients receiving propranolol therapy for infantile hemangiomas between October 2018-March 2021 at the Children's Hospital of Philadelphia. Patients were categorized by initial propranolol dosage: 1 or 2 mg/kg/day. The primary outcome measures included parent-reported adverse events, hypotension (defined by the Pediatric Advanced Life Support criteria), and bradycardia (defined as <1st percentile for age) following propranolol initiation. RESULTS: Out of the 244 patients identified, 123 were initiated at the 1 mg/kg/day dose, and 121 at the 2 mg/kg/day dose. There was no significant difference in the incidence of adverse events between the two groups (p = .057). Additionally, among patients initiated at 2 mg/kg/day, there were no significant differences in the incidence of age-related or weight-related adverse events for those younger than 2 months or those in the 1st or 2nd quartile for weight (p = .53). CONCLUSION: Infants and children initiated at 2 mg/kg/day did not demonstrate an increased incidence of adverse events associated with propranolol compared to those initiated at 1 mg/kg/day. These findings provide clinical evidence for the practice of accelerated propranolol initiation dosing.


Assuntos
Propranolol , Humanos , Propranolol/administração & dosagem , Propranolol/efeitos adversos , Estudos Retrospectivos , Lactente , Feminino , Masculino , Hemangioma/tratamento farmacológico , Pré-Escolar , Relação Dose-Resposta a Droga , Bradicardia/induzido quimicamente , Esquema de Medicação , Hipotensão/induzido quimicamente , Antagonistas Adrenérgicos beta/administração & dosagem , Antagonistas Adrenérgicos beta/efeitos adversos , Neoplasias Cutâneas/tratamento farmacológico , Recém-Nascido
5.
J Perioper Pract ; 34(7-8): 241-247, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343016

RESUMO

Anaesthesiologists commonly use intravenous labetalol to adjust patient haemodynamics during surgical procedures. Cases of profound hypotension after continuous labetalol infusions have been reported; however, there is limited evidence regarding the safety of intraoperative labetalol boluses. This audit examined the frequency of postoperative hypotension and bradycardia in 292 adult non-cardiac surgery patients treated with intraoperative labetalol boluses. Blood pressure and heart rate data were collected from the post-anaesthesia care unit and on the floor units for 24 hours after surgery. The median total intraoperative labetalol dose was 10mg. A total of 30/292 patients had all-cause postoperative hypotension within 24 hours of surgery, 26 of which had other medical or surgical precipitants. Fifteen patients developed bradycardia. There were no deaths or intensive care unit admissions attributed to labetalol. This audit demonstrates a low risk of all-cause postoperative hypotension (10%) and bradycardia (5%) after the use of small IV doses of intraoperative labetalol.


Assuntos
Hipotensão , Labetalol , Humanos , Labetalol/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Hemodinâmica/efeitos dos fármacos , Cuidados Intraoperatórios/métodos , Idoso , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Auditoria Médica , Adulto , Bradicardia/induzido quimicamente , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/uso terapêutico
6.
Drug Des Devel Ther ; 18: 443-452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38370564

RESUMO

Purpose: Dexmedetomidine (Dex) is a potent and highly selective α2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC). Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 µg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded. Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P>0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P<0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P<0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P<0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P<0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P<0.05 for all). Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 µg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.


Assuntos
Colecistectomia Laparoscópica , Dexmedetomidina , Humanos , Bradicardia/induzido quimicamente , Estudos Prospectivos , Anestesia Geral , Dor Pós-Operatória/tratamento farmacológico , Pré-Medicação/métodos , Método Duplo-Cego
7.
BMC Anesthesiol ; 23(1): 406, 2023 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-38082217

RESUMO

BACKGROUND: Sympathetic stimulation associated with laryngoscopy and endotracheal intubation (ETI) may lead to adverse cardio-/cerebro-vascular events in susceptible patients. Nebulization is a novel route for dexmedetomidine administration providing a large surface area for absorption while avoiding bradycardia and hypotension associated with intravenous route. We aimed to evaluate the efficacy and safety of dexmedetomidine nebulization for attenuating hemodynamic response to ETI in adult patients undergoing surgery under general anaesthesia. METHODS: This systematic review was registered prospectively in the International Prospective Register of Systematic Reviews (CRD42023403624). PubMed, Embase (OvidSP), Cochrane library, Scopus (Elsevier), Web of Science (Clarivate) and Google Scholar were systematically searched from database inception until March 31, 2023. Two reviewers independently screened titles, abstracts and then full text against pre-specified eligibility criteria. Randomized controlled trials (RCTs) assessing effect of dexmedetomidine nebulization on hemodynamic response to ETI in adult patients undergoing surgeries under general anaesthesia were included. All studies reporting heart rate and systolic blood pressure at baseline and various time points after ETI were included. A pre-piloted data extraction form, Cochrane revised risk-of-bias tool (ROB 2) tool, GRADE approach and RevMan 5.4.1 (Cochrane Collaboration, Copenhagen, Denmark) were used for data extraction, risk of bias assessment, rating certainty of evidence and data synthesis respectively. Mean difference and relative risk with 95% Confidence Interval (CI) were used for continuous and dichotomous variables respectively. RESULTS: Six RCTs randomized 480 patients with ASA I/II patients aged < 60 years of age and undergoing elective surgeries to receive either dexmedetomidine (n = 240) or saline nebulization (n = 240). Except for one RCT which used 2 µg/kg, all other RCTs used dexmedetomidine dose of 1 µg /kg. Heart rate, systolic, diastolic and mean blood pressure were significantly lower in the dexmedetomidine group at all the measured time points after laryngoscopy and ETI with the only exception being systolic blood pressure at 3 min [mean difference -13.86 (95% CI -30.01 to 2.99), p = 0.09]. Bradycardia and hypotension as adverse effects were absent across the included studies. However, only one-third of the included studies had a low risk of bias and strength of evidence was very low according to the GRADE assessment. CONCLUSIONS: Compared to placebo, premedication with dexmedetomidine nebulization was associated with lower HR and BP following ETI without any risk of bradycardia and hypotension. However, the strength of evidence was very poor and came from just one country. Future well designed and conducted studies in different populations are warranted. TRIAL REGISTRATION: PROSPERO Registration number: CRD42023403624.


Assuntos
Dexmedetomidina , Hipotensão , Adulto , Humanos , Pessoa de Meia-Idade , Dexmedetomidina/farmacologia , Laringoscopia/efeitos adversos , Bradicardia/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Anestesia Geral/efeitos adversos , Hemodinâmica , Hipotensão/induzido quimicamente , Intubação Intratraqueal/efeitos adversos
8.
Medicine (Baltimore) ; 102(34): e34775, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37653784

RESUMO

RATIONALE: Despite various advantages of laparoscopic surgical procedures, artificial pneumoperitoneum might lead to hemodynamic fluctuations including severe bradycardia and cardiac arrest. Atropine is usually proposed to treat intraoperative severe bradycardia ( < 40 beats per minute). However, atropine could induce ventricular arrhythmias, which might be life-threatening in severe case. PATIENT CONCERNS: Here, we reported a 41-year-old female who was diagnosed with gallbladder polyps and was scheduled for laparoscopic cholecystectomy under general anesthesia. DIAGNOSES: Bradycardia occurred suddenly during the operation and atropine was injected intravenously. Eventually the patient developed ventricular tachycardia and acute heart failure. INTERVENTIONS: We organized an urgent consultation and the patient was treated immediately. OUTCOMES: Fortunately, the patient experienced no complications after timely diagnosis and treatment. After 6 months of follow-up, her New York Heart Association classification was I with no complications. LESSONS: This case highlighted that the administration of atropine to treat bradycardia may lead to ventricular tachycardia and acute heart failure, and anesthesiologists should remain vigilant to avoid potentially life-threatening consequences.


Assuntos
Insuficiência Cardíaca , Taquicardia Ventricular , Humanos , Feminino , Adulto , Bradicardia/induzido quimicamente , Atropina/uso terapêutico , Arritmias Cardíacas , Taquicardia Ventricular/induzido quimicamente , Taquicardia Ventricular/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico
9.
J Surg Oncol ; 128(7): 1141-1149, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37702402

RESUMO

INTRODUCTION: Hyperthermic intraoperative cisplatin (HIOC) is associated with acute kidney injury (AKI). Administration of high-dose magnesium attenuates cisplatin-induced AKI (CP-AKI) in animal models but has not been rigorously examined in humans. METHODS: We tested the feasibility and safety of different doses of magnesium in mesothelioma patients receiving HIOC. In Pilot Study 1, we administered a 36-h continuous infusion of magnesium at 0.5 g/h, targeting serum magnesium levels between 3 and 4.8 mg/dL. In Pilot Study 2A, we administered a 6 g bolus followed by an infusion starting at 2 g/h, titrated to achieve levels between 4 and 6 mg/dL. We eliminated the bolus in Pilot Study 2B. RESULTS: In Pilot Study 1, all five patients enrolled completed the study; however, median postoperative Mg levels were only 2.4 mg/dL. In Pilot Study 2A, two of four patients (50%) were withdrawn due to bradycardia during the bolus. In Pilot Study 2B, two patients completed the study whereas two developed postoperative bradycardia attributed to the magnesium. CONCLUSIONS: A 0.5 g/h infusion for 36 h did not achieve therapeutic magnesium levels, while an infusion at 2 g/h was associated with bradycardia. These studies informed the design of a randomized clinical trial testing whether intravenously Mg attenuates HIOC-associated AKI.


Assuntos
Injúria Renal Aguda , Mesotelioma Maligno , Mesotelioma , Humanos , Cisplatino/efeitos adversos , Projetos Piloto , Magnésio/uso terapêutico , Bradicardia/induzido quimicamente , Bradicardia/tratamento farmacológico , Mesotelioma/tratamento farmacológico , Mesotelioma Maligno/induzido quimicamente , Mesotelioma Maligno/tratamento farmacológico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/tratamento farmacológico
10.
Acta Paediatr ; 112(11): 2338-2345, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37531450

RESUMO

AIM: This study aimed to assess the safety of a commonly used sedative, dexmedetomidine in neonates and infants during intensive care. METHODS: A retrospective cohort study was conducted in the paediatric intensive care unit at Oulu University Hospital. The study population consisted of all children from birth up to 6 months of age who received dexmedetomidine during 2010-2016. Adverse cardiovascular outcomes were defined as abnormal heart rates or blood pressure values according to the Paediatric Early Warning Score. RESULTS: Of the 172 infants, 56% had congenital malformation, and 48% had undergone surgery. Neonates and 1-3-month-olds experienced bradycardia (86% vs. 73% in 1-3-month-olds and 50% in 3-6-month-olds, p = 0.001) and severe bradycardia (17% vs. 14% in 1-3-month-olds and 0% in 3-6-month-olds, p = 0.005) more often than older patients. The median maximum rate of dexmedetomidine infusion was 0.86 µg/kg/h (IQR = 0.60-1.71 µg/kg/h). A dose-dependent increase in bradycardia and severe hypotension was found. Adverse cardiovascular events were managed with additional fluid boluses and discontinuation of the infusion. CONCLUSION: Adverse cardiovascular events were common during dexmedetomidine administration in neonates and infants. Lower dexmedetomidine doses may be required in sedating neonates.


Assuntos
Dexmedetomidina , Recém-Nascido , Criança , Humanos , Lactente , Dexmedetomidina/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Estudos Retrospectivos , Hipnóticos e Sedativos/efeitos adversos , Cuidados Críticos
11.
Ecotoxicol Environ Saf ; 263: 115225, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37418940

RESUMO

Bisphenol A (BPA) and its analogs, such as bisphenol F (BPF), bisphenol AF (BPAF), and bisphenol B (BPB), are often simultaneously detected in environmental and human specimens. Thus, assessing the toxicity of bisphenol (BP) mixtures is more relevant than assessing that of each BP type. Here, we found that BPs, individually or in a mixture, concentration-dependently and additively increased the mortality of zebrafish embryos (ZFEs) at 96 h post fertilization (hpf) and induced bradycardia (i.e., reduced heart rate) at 48 hpf, indicating their cardiotoxic potency. BPAF was the most potent, followed by BPB, BPA, and BPF. We then explored the mechanism underlying BP-induced bradycardia in ZFEs. Although BPs increased the mRNA expression of the estrogen-responsive gene, treatment with the estrogen receptor inhibitor ICI 182780 did not prevent BP-induced bradycardia. Because they did not change cardiomyocyte counts or heart development-related gene expression, BPs might not affect cardiomyocyte development. By contrast, BPs might impair calcium homeostasis during cardiac contraction and relaxation through the downregulation of the expression of the mRNAs for the pore-forming subunit of L-type Ca2+ channel (LTCC; cacna1c) and sarco/endoplasmic reticulum Ca2+-ATPase (SERCA; atp2a2a). BPs reduced SERCA activity significantly. BPs also potentiated the cardiotoxicity induced by the LTCC blocker nisoldipine, conceivably by inhibiting SERCA activity. In conclusion, BPs additively induced bradycardia in ZFEs, possibly by impeding calcium homeostasis during cardiac contraction and relaxation. BPs also potentiated the cardiotoxicity of calcium channel blockers.


Assuntos
Canais de Cálcio , Peixe-Zebra , Animais , Humanos , Canais de Cálcio/genética , Bradicardia/induzido quimicamente , Cálcio , Cardiotoxicidade , Compostos Benzidrílicos/toxicidade
12.
Anaesthesiol Intensive Ther ; 55(1): 46-51, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37306271

RESUMO

INTRODUCTION: Heart transplant recipients present unique perioperative challenges for surgery. Specifically, autonomic system denervation has significant implications for commonly used perioperative drugs. This study investigates neuromuscular blocking antagonists in this population when undergoing subsequent non-cardiac surgery. MATERIAL AND METHODS: A retrospective review was performed for the period 2015-2019 across our health care enterprise. Patients with previous orthotopic heart transplant and subsequent non-cardiac surgery were identified. A total of 185 patients were found, 67 receiving neostigmine (NEO) and 118 receiving sugammadex (SGX). Information of patient characteristics, prior heart transplant, and subsequent non-cardiac surgery was collected. Our primary outcome was the incidence of bradycardia (heart rate < 60 bpm) and/or hypotension (mean blood pressure (MAP) < 65 mmHg) following neuromuscular blockade reversal. Secondary outcomes included need of intra-operative inotropic agents, arrhythmia, cardiac arrest, hospital length of stay (hLOS), ICU admission, and death within 30 postoperative days. RESULTS: In unadjusted analysis, no significant differences were found between the two groups in change in heart rate [0 (-26, 14) vs. 1 (-19, 10), P = 0.59], change in MAP [0 (-22, 28) vs. 0 (-40, 47), P = 0.96], hLOS [2 days (1, 72) vs. 2 (0, 161), P = 0.92], or intraoperative hypotension [4 (6.0%) vs. 5 (4.2%), OR = 0.70, P = 0.60] for NEO and SGX respectively. After multivariable analysis, the results were similar for change in heart rate ( P = 0.59) and MAP ( P = 0.90). CONCLUSIONS: No significant differences in the incidence of bradycardia and hypotension were found in the NEO versus SGX groups. NEO and SGX may have similar safety profiles in patients with prior heart transplant undergoing non-cardiac surgery.


Assuntos
Anestésicos , Transplante de Coração , Hipotensão , Bloqueio Neuromuscular , Doenças Neuromusculares , Humanos , Neostigmina , Sugammadex , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia
14.
Target Oncol ; 18(4): 571-583, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37341856

RESUMO

BACKGROUND: Randomized trials have demonstrated that anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) can be safe and efficacious treatments for patients with ALK-positive advanced non-small-cell lung cancer (aNSCLC). However, their safety, tolerability, effectiveness, and patterns of use in real-world patients remain understudied. OBJECTIVE: We sought to assess the overall treatment pattern characteristics, safety, and effectiveness outcomes of real-world patients with ALK-positive aNSCLC receiving ALK TKIs. PATIENTS AND METHODS: This retrospective cohort study using electronic health record data included adult patients with ALK-positive aNSCLC receiving ALK TKIs between January 2012 and November 2021 at a large tertiary medical center, University of California, San Francisco (UCSF), with alectinib or crizotinib as the initial ALK TKI therapy. Our primary endpoints included the incidence of treatment changes (treatment dose adjustments, interruptions, and discontinuations) during the initial ALK TKI treatment, the count and type of subsequent treatments, rates of serious adverse events (sAEs), and major adverse events (mAEs) leading to any ALK TKI treatment changes. Secondary endpoints included the hazard ratios (HRs) for median mAE-free survival (mAEFS), real-world progression-free survival (rwPFS), and overall survival (OS) when comparing alectinib with crizotinib. RESULTS: The cohort consisted of 117 adult patients (70 alectinib and 47 crizotinib) with ALK-positive aNSCLC, with 24.8%, 17.9%, and 6.0% experiencing treatment dose adjustments, interruptions, and discontinuation, respectively. Of the 73 patients whose ALK TKI treatments were discontinued, 68 received subsequent treatments including newer generations of ALK TKIs, immune checkpoint inhibitors, and chemotherapies. The most common mAEs were rash (9.9%) and bradycardia (7.0%) for alectinib and liver toxicity (19.1%) for crizotinib. The most common sAEs were pericardial effusion (5.6%) and pleural effusion (5.6%) for alectinib and pulmonary embolism (6.4%) for crizotinib. Patients receiving alectinib versus crizotinib as their first ALK TKI treatment experienced significantly prolonged median rwPFS (29.3 versus 10.4 months) with an HR of 0.38 (95% CI 0.21-0.67), while prolonged median mAEFS (not reached versus 91.3 months) and OS (54.1 versus 45.8 months) were observed in patients receiving alectinib versus crizotinib but did not reach statistical significance. Yet, it is worth noting that there was a high degree of cross-over post-progression, which could significantly confound the overall survival measures. CONCLUSIONS: We found that ALK TKIs were highly tolerable, and alectinib was associated with favorable survival outcomes with longer time to adverse events (AE) requiring medical interventions, disease progression, and death, in the context of real-world use. Proactive monitoring for adverse events such as rash, bradycardia, and hepatotoxicity may help further promote the safe and optimal use of ALK TKIs in the treatment of patients with aNSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Crizotinibe/farmacologia , Crizotinibe/uso terapêutico , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Bradicardia/induzido quimicamente , Bradicardia/tratamento farmacológico , Quinase do Linfoma Anaplásico/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases
15.
Drug Des Devel Ther ; 17: 1233-1243, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37125082

RESUMO

Purpose: This study aimed to compare the cardiopulmonary safety of remimazolam and propofol in patients undergoing cervical conization. Methods: This was a single-blind, parallel, randomized controlled study. A total of 204 patients scheduled for day surgery of cold knife cervical conization received either remimazolam-alfentanil anesthesia (remimazolam group) or propofol-alfentanil anesthesia (propofol group). The primary outcome was the incidence of intraoperative cardiopulmonary adverse events (a composite outcome of hypotension, bradycardia and hypoxemia). The occurrence of hypotension, bradycardia, hypoxemia and the degree of body movement were secondary outcomes, as well as the moment at which consciousness was lost, the interval between the end of anesthesia and the operating room's release of the patient, and the overall dosage of alfentanil administered during the procedure. Results: The incidence of intraoperative cardiopulmonary adverse events was 45 (44.1%) in the remimazolam group and 72 (70.6%) in the propofol group (absolute risk difference [95% CI], -26.47% [-39.55% to -13.39%]; odds ratio (OR) [95% CI], 0.43 [0.28 to 0.65]; P < 0.001). The remimazolam group showed lower incidences of hypotension and hypoxemia compared to the propofol group (P = 0.01 for both). No significant differences were observed in the overall alfentanil dosages administered, bradycardia, bodily movement, or time to losing consciousness between the two groups. Conclusion: In patients who underwent cold knife cervical conization, remimazolam-alfentanil anesthesia was associated with a reduced incidence of intraoperative cardiopulmonary adverse events compared with propofol-alfentanil anesthesia.


Assuntos
Hipotensão , Propofol , Humanos , Propofol/efeitos adversos , Alfentanil/efeitos adversos , Anestésicos Intravenosos , Conização , Bradicardia/induzido quimicamente , Método Simples-Cego , Benzodiazepinas , Hipotensão/induzido quimicamente , Hipóxia
16.
Zhonghua Yi Xue Za Zhi ; 103(17): 1303-1309, 2023 May 09.
Artigo em Chinês | MEDLINE | ID: mdl-37150679

RESUMO

Objective: To investigate the effects of remimazolam versus propofol on postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Methods: A total of 108 elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy under general anesthesia in the Affiliated Cancer Hospital of Zhengzhou University from May to October 2022 were prospectively included. The participants were divided into two groups by the random number table method: remimazolam group (R group, n=54) and propofol group (P group, n=54). There were 54 cases in the R group, with 35males and 19 females, and aged (65.4±3.1) years. Meanwhile, there were 54 cases in the P group, with 33males and 21 females, and aged (64.5±3.0) years. Anesthesia was induced as follows: remimazolam 0.2-0.3 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in R group, while propofol 1-2 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in P group. Subsequently, anesthesia was maintained as follows: remimazolam 0.4-1.0 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group R, while propofol 4-10 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group P. Bispectral index (BIS) was maintained at 45-60 during operation. The main outcome measures were the 15-item quality of recovery (QoR-15) scores 1 day before surgery, 1 day and 3 days after surgery. Secondary outcome measures included mean arterial pressure (MAP), heart rate and pulse oxygen saturation (SpO2) recorded 5 min before anesthesia induction (T0), 1 min after induction (T1), 1 min after endotracheal intubation (T2), immediately after skin incision (T3) and tracheal extubation (T4). The incidence of bradycardia and hypotension and the frequency of application of vasoactive drugs during anesthesia were recorded. Restlessness score (RS) and Ramsay sedation scale during the awakening period were recorded. Emergence time, tracheal extubation time, duration of postanesthesia care unit (PACU) stay and postoperative length of hospital stay were recorded. The incidence of postoperative pulmonary infection and other complications were also recorded. Results: The QoR-15 scale scores [M (Q1, Q3)] of R group 1 day and 3 days after surgery were 114.0 (109.0, 118.3) and 131.0 (127.8, 133.0), which were higher than those of P group [106.0 (101.0, 112.0) and 127.0 (125.0, 129.3)] (both P<0.001). The incidence of bradycardia, hypotension and the frequency of application of vasoactive drugs of R group during anesthesia were 5.6% (3/54), 35.2% (19/54) and 27.8% (15/54), which were lower than those in P group [33.3% (18/54), 63.0% (34/54) and 55.6% (30/54), respectively] (all P<0.05). RS score during the awakening period in R group was 0.9±0.5, which was lower than that of P group (1.1±0.6) (P=0.046). Emergence time, tracheal extubation time and postoperative length of hospital stay of R group were (15.4±4.9) min, (16.6±4.7) min and (11.6±1.4) d, which were shorter than those of P group [(26.2±6.4) min, (27.8±5.8) min and (12.6±1.3) d] (all P<0.05). There were no statistically significant differences in Ramsay scores during the awakening period, duration of PACU stay and the incidence of postoperative complications (all P>0.05). Conclusions: Both remimazolam and propofol can achieve satisfactory postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Remimazolam has more stable hemodynamics and lower incidence of adverse reactions.


Assuntos
Hipotensão , Laparoscopia , Propofol , Idoso , Feminino , Humanos , Remifentanil , Bradicardia/induzido quimicamente , Esofagectomia , Anestesia Geral , Complicações Pós-Operatórias , Hipotensão/induzido quimicamente
17.
Taiwan J Obstet Gynecol ; 62(2): 239-251, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36965890

RESUMO

This study investigated the efficacy and safety of intravenous dexmedetomidine as an adjuvant to general anesthesia in patients undergoing gynecological surgery. We systemically searched for randomized controlled trials (RCTs), and performed a meta-analysis on studies that met the inclusion criteria. The primary outcomes were postoperative nausea and vomiting (PONV), bradycardia, hypotension, and 24 h opioid consumption. The secondary outcomes include postoperative shivering, postoperative pain score, intraoperative anesthetic consumption, extubation time, postoperative sedation, and the time to first flatus. Twenty-five RCTs were included in this study. Meta-analysis showed that intravenous dexmedetomidine significantly reduced the risk of PONV (RR, 0.57 [0.47, 0.68]) and postoperative shivering (RR: 0.31 [0.22, 0.42]), 24 h opioid consumption (Mean Difference: - 4.85 mg [-8.60, -1.11]) and postoperative pain score within 24 h. However, these benefits were at the cost of increased bradycardia (RR, 3.21 [2.41, 4.28]) and hypotension (RR, 2.17 [1.50, 3.14]). Notably, no serious adverse effects were reported in any of the included studies. Thus, our study showed that intravenous dexmedetomidine provided significant antiemetic and anti-shivering effects and moderate analgesic effects in patients that underwent gynecological surgery. However, its benefits should be weighed against the significantly increased risk of bradycardia and hypotension.


Assuntos
Dexmedetomidina , Hipotensão , Humanos , Feminino , Dexmedetomidina/efeitos adversos , Analgésicos Opioides , Náusea e Vômito Pós-Operatórios/induzido quimicamente , Náusea e Vômito Pós-Operatórios/prevenção & controle , Bradicardia/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Anestesia Geral/efeitos adversos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/prevenção & controle , Adjuvantes Imunológicos , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos
18.
Braz. J. Anesth. (Impr.) ; 73(1): 101-103, Jan.-Feb. 2023. graf
Artigo em Inglês | LILACS | ID: biblio-1420643

RESUMO

Abstract Sugammadex is a distinctive neuromuscular reversal drug that acts by encapsulating the neuromuscular relaxant molecule and dislodging it from its site of action. Sugammadex has been approved for pediatric patients over 2 years of age. Although arrhythmias have been reported, there is no report of adverse effects in healthy children, such as severe bradycardia requiring intervention. We report two cases of severe bradycardia immediately after the administration of sugammadex in healthy children. Our aim is to alert to the occurrence of one of the most severe adverse effects of sugammadex, in the healthy pediatric population as well.


Assuntos
Humanos , Criança , Fármacos Neuromusculares não Despolarizantes , Bloqueio Neuromuscular , Bradicardia/induzido quimicamente , Sugammadex/efeitos adversos
20.
J Perioper Pract ; 33(7-8): 211-216, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35285310

RESUMO

BACKGROUND: Cardiovascular effects for drugs such as hyoscine butylbromide are poorly documented in the literature, unlike atropine, which is considered the antimuscarinic of choice in the presence of intraoperative bradycardia. AIM: The aim of the study was to describe the dose-related cardiovascular effect of hyoscine butylbromide in patients between 18 and 65 years of age, with low perioperative risk undergoing elective surgery under general anaesthesia on an outpatient basis or hospitalised at our institution between 1 January and 31 May 2019. METHODS: Descriptive, cross-sectional, retrospective study; 28 patients with low perioperative risk who underwent general anaesthesia were selected. Changes in heart rate and blood pressure were analysed during the first 6 minutes after the administration of hyoscine butylbromide. The data obtained was recorded in a Microsoft Excel database and analysed using the Excel analysis tool and IBM SPSS. RESULTS: The average dose of 0.15mg/kg of hyoscine butylbromide achieved an increase in heart rate and mean arterial pressure in 96% and 92.8%, respectively, in the first 6 minutes after the administration. Significant changes in heart rate and blood pressure were obtained during the first 6 minutes at doses between 0.05mg/kg and 0.15mg/kg. CONCLUSION: Hyoscine butylbromide generates positive effects on the heart rate and blood pressure of patients under general anaesthesia, representing a possible alternative in the management of intraoperative bradycardia.


Assuntos
Bradicardia , Escopolamina , Humanos , Bradicardia/induzido quimicamente , Estudos Retrospectivos , Estudos Transversais , Brometo de Butilescopolamônio/efeitos adversos , Anestesia Geral
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