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2.
Cochrane Database Syst Rev ; 10: CD011064, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33000470

RESUMO

BACKGROUND: Calcium channel blockers (CCBs) are used to manage hypertension which is highly prevalent among people with chronic kidney disease (CKD). The treatment for hypertension is particularly challenging in people undergoing dialysis. OBJECTIVES: To assess the benefits and harms of calcium channel blockers in patients with chronic kidney disease requiring dialysis. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies to 27 April 2020 through contact with the Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: All randomised controlled trials (RCTs) and quasi-RCTs that compared any type of CCB with other CCB, different doses of the same CCB, other antihypertensives, control or placebo were included. The minimum study duration was 12 weeks. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random-effects model and results expressed as risk ratio (RR), risk difference (RD) or mean difference (MD) with 95% confidence intervals (CI). MAIN RESULTS: This review included 13 studies (24 reports) randomising 1459 participants treated with long-term haemodialysis. Nine studies were included in the meta-analysis (622 participants). No studies were performed in children or in those undergoing peritoneal dialysis. Overall, risk of bias was assessed as unclear to high across most domains. Random sequence generation and allocation concealment were at low risk of bias in eight and one studies, respectively. Two studies reported low risk methods for blinding of participants and investigators, and outcome assessment was blinded in 10 studies. Three studies were at low risk of attrition bias, eight studies were at low risk of selective reporting bias, and five studies were at low risk of other potential sources of bias. Overall, the certainty of the evidence was low to very low for all outcomes. No events were reported for cardiovascular death in any of the comparisons. Other side effects were rarely reported and studies were not designed to measure costs. Five studies (451 randomised adults) compared dihydropyridine CCBs to placebo or no treatment. Dihydropyridine CCBs may decrease predialysis systolic (1 study, 39 participants: MD -27.00 mmHg, 95% CI -43.33 to -10.67; low certainty evidence) and diastolic blood pressure level (2 studies, 76 participants; MD -13.56 mmHg, 95% CI -19.65 to -7.48; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Dihydropyridine CCBs may make little or no difference to occurrence of intradialytic hypotension (2 studies, 287 participants; RR 0.54, 95% CI 0.25 to 1.15; I2 = 0%, low certainty evidence) compared to placebo or no treatment. Other side effects were not reported. Eight studies (1037 randomised adults) compared dihydropyridine CCBs to other antihypertensives. Dihydropyridine CCBs may make little or no difference to predialysis systolic (4 studies, 180 participants: MD 2.44 mmHg, 95% CI -3.74 to 8.62; I2 = 0%, low certainty evidence) and diastolic blood pressure (4 studies, 180 participants: MD 1.49 mmHg, 95% CI -2.23 to 5.21; I2 = 0%, low certainty evidence) compared to other antihypertensives. There was no evidence of a difference in the occurrence of intradialytic hypotension (1 study, 92 participants: RR 2.88, 95% CI 0.12 to 68.79; very low certainty evidence) between dihydropyridine CCBs to other antihypertensives. Other side effects were not reported. Dihydropyridine CCB may make little or no difference to predialysis systolic (1 study, 40 participants: MD -4 mmHg, 95% CI -11.99 to 3.99; low certainty evidence) and diastolic blood pressure (1 study, 40 participants: MD -3.00 mmHg, 95% CI -7.06 to 1.06; low certainty evidence) compared to non-dihydropyridine CCB. There was no evidence of a difference in other side effects (1 study, 40 participants: RR 0.13, 95% CI 0.01 to 2.36; very low certainty evidence) between dihydropyridine CCB and non-dihydropyridine CCB. Intradialytic hypotension was not reported. AUTHORS' CONCLUSIONS: The benefits of CCBs over other antihypertensives on predialysis blood pressure levels and intradialytic hypotension among people with CKD who required haemodialysis were uncertain. Effects of CCBs on other side effects and cardiovascular death also remain uncertain. Dihydropyridine CCBs may decrease predialysis systolic and diastolic blood pressure level compared to placebo or no treatment. No studies were identified in children or peritoneal dialysis. Available studies have not been designed to measure the effects on costs. The shortcomings of the studies were that they recruited very few participants, had few events, had very short follow-up periods, some outcomes were not reported, and the reporting of outcomes such as changes in blood pressure was not done uniformly across studies. Well-designed RCTs, conducted in both adults and children with CKD requiring both haemodialysis and peritoneal dialysis, evaluating both dihydropyridine and non-dihydropyridine CCBs against other antihypertensives are required. Future research should be focused on outcomes relevant to patients (including death and cardiovascular disease), blood pressure changes, risk of side effects and healthcare costs to assist decision-making in clinical practice.


Assuntos
Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Di-Hidropiridinas/uso terapêutico , Hipertensão/tratamento farmacológico , Diálise Renal , Insuficiência Renal Crônica/terapia , Adulto , Viés , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Di-Hidropiridinas/efeitos adversos , Humanos , Hipotensão/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como Assunto , Insuficiência Renal Crônica/complicações
3.
Medicine (Baltimore) ; 99(40): e22536, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019461

RESUMO

RATIONALE: Paroxysmal autonomic instability with dystonia (PAID) is an underdiagnosed syndrome that describes a collection of symptoms following diverse cerebral insults, such as traumatic brain injury, hydrocephalus, hemorrhagic stroke, or brain anoxia. It is manifested by systemic high blood pressure, hyperthermia, tachycardia, tachypnea, diaphoresis, intermittent agitation, and certain forms of dystonia. PATIENT CONCERNS: A semi-comatose 46-year-old man was transferred from the regional rehabilitation hospital with various complaints involving fluctuating vital signs, including uncontrolled hyperthermia, hypertension, tachycardia, and tachypnea, and dystonia in all extremities. The patient underwent brain surgery for astrocytoma in 1996. The patient also had a history of first ischemic stroke on the basal ganglia in 2008 and a second one in the same area in 2017. DIAGNOSIS: The laboratory, electrocardiography, and radiologic findings were normal. Brain imaging indicated an old infarction on the basal ganglia with hydrocephalus. Tractography using diffusion tensor imaging showed discontinuity of multiple tracts, and electrophysiologic tests, such as evoked potentials, displayed an absent response. Based on the dysautonomic symptoms and brain evaluations, the physiatrist diagnosed the patient with PAID. INTERVENTIONS: Bromocriptine, propranolol, and clonazepam were administered sequentially, but autonomic instability persisted. Then, intravenous opioid was administered, and fluctuations in body temperature, heart rate, and respiratory rate, as well as decerebrate-type dystonia were improved. However, simultaneously, drug-induced severe hypotension developed (systolic blood pressure, 57 mm Hg). Subsequently, a transdermal opioid (fentanyl) patch for PAID was applied once every 3 days. OUTCOMES: Ultimately, all vital signs and dystonia were managed without further complications, and the patient was discharged. LESSONS: A patient diagnosed with PAID following multiple cerebral insults was observed, whose condition was controlled by application of opioid patch rather than by intravenous or oral routes. A transdermal opioid patch, such as fentanyl patch, can thus be effective in the treatment of patients with PAID following multiple cerebral insults.


Assuntos
Analgésicos Opioides/uso terapêutico , Doenças do Sistema Nervoso Autônomo/tratamento farmacológico , Distonia/diagnóstico , Fentanila/uso terapêutico , Doenças do Sistema Nervoso Autônomo/diagnóstico , Doenças do Sistema Nervoso Autônomo/fisiopatologia , Gânglios da Base/patologia , Isquemia Encefálica/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Distonia/etiologia , Febre/diagnóstico , Febre/etiologia , Humanos , Hidrocefalia/etiologia , Hipertensão/diagnóstico , Hipertensão/etiologia , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Síndrome , Taquicardia/diagnóstico , Taquicardia/etiologia , Taquipneia/diagnóstico , Taquipneia/etiologia , Adesivo Transdérmico/efeitos adversos , Resultado do Tratamento
4.
Toxicon ; 186: 58-66, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32755648

RESUMO

Envenomation by coralsnakes (Micrurus spp.) is characterized by blockade of peripheral neurotransmission mediated by the presence of α- and ß-neurotoxins. However, little is known about their cardiovascular activity. Micrurus lemniscatus lemniscatus is a coralsnake found in the Amazon basin and occasionally causes envenomation in humans. In this study, we examined the hemodynamic, vascular and atrial responses to M. l. lemniscatus venom. Anesthetized rats were used for hemodynamic and electrocardiogram (ECG) recordings; in vitro experiments were carried out in rat isolated thoracic aorta and atria preparations. In vivo, venom (0.1 and 0.3 mg/kg) caused immediate and persistent hypotension that was maximal within the first minute with both doses being lethal after ~40 and ~20 min, respectively. ECG, heart and respiratory rates were not altered during the transient hypotension phase induced by venom but all altered prior to death. There was no evidence of myonecrosis in cardiac muscle tissue, pulmonary hemorrhage nor thrombosis in anesthetized rats exposed to venom. In vitro, venom (10 µg/ml) did not contract aortic strips nor affected the maximal responses to pre-contraction with phenylephrine (PE, 0.0001-30 µM) in strips with and without endothelium. However, venom (10 µg/ml) relaxed aortic strips with endothelium pre-contracted with PE. In aortic strips pre-contracted with PE, venom prevented acetylcholine (0.0001-30 µM)-induced relaxation in strips with endothelium without affecting relaxation induced by sodium nitroprusside (0.1-100 nM) in strips without endothelium. Venom (30 µg/ml) produced a transient increase of atrial contractile force without affecting atrial rate. Taken together these findings indicate a predominantly vascular action of the venom, most likely involving toxins interacting with muscarinic receptors.


Assuntos
Sistema Cardiovascular/efeitos dos fármacos , Cobras Corais , Venenos Elapídicos/toxicidade , Coração/efeitos dos fármacos , Animais , Hemodinâmica , Hipotensão/induzido quimicamente , Miocárdio , Ratos
5.
JACC Heart Fail ; 8(10): 789-799, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32641226

RESUMO

The PARADIGM-HF (Prospective Comparison of Angiotensin II Receptor Blocker Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) trial reported that sacubitril/valsartan (S/V), an angiotensin receptor-neprilysin inhibitor, significantly reduced mortality and heart failure (HF) hospitalization in HF patients with a reduced ejection fraction (HFrEF). However, fewer than 1% of patients in the PARADIGM-HF study had New York Heart Association (NYHA) functional class IV symptoms. Accordingly, data that informed the use of S/V among patients with advanced HF were limited. The LIFE (LCZ696 in Hospitalized Advanced Heart Failure) study was a 24-week prospective, multicenter, double-blinded, double-dummy, active comparator trial that compared the safety, efficacy, and tolerability of S/V with those of valsartan in patients with advanced HFrEF. The trial planned to randomize 400 patients ≥18 years of age with advanced HF, defined as an EF ≤35%, New York Heart Association functional class IV symptoms, elevated natriuretic peptide concentration (B-type natriuretic peptide [BNP] ≥250 pg/ml or N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥800 pg/ml), and ≥1 objective finding of advanced HF. Following a 3- to 7-day open label run-in period with S/V (24 mg/26 mg twice daily), patients were randomized 1:1 to S/V titrated to 97 mg/103 mg twice daily versus 160 mg of V twice daily. The primary endpoint was the proportional change from baseline in the area under the curve for NT-proBNP levels measured through week 24. Secondary and tertiary endpoints included clinical outcomes and safety and tolerability. Because of the COVID-19 pandemic, enrollment in the LIFE trial was stopped prematurely to ensure patient safety and data integrity. The primary analysis consists of the first 335 randomized patients whose clinical follow-up examination results were not severely impacted by COVID-19. (Entresto [LCZ696] in Advanced Heart Failure [LIFE STUDY] [HFN-LIFE]; NCT02816736).


Assuntos
Aminobutiratos/uso terapêutico , Antagonistas de Receptores de Angiotensina/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Tetrazóis/uso terapêutico , Betacoronavirus , Cardiotônicos/uso terapêutico , Infecções por Coronavirus , Relação Dose-Resposta a Droga , Método Duplo-Cego , Término Precoce de Ensaios Clínicos , Taxa de Filtração Glomerular , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Transplante de Coração , Coração Auxiliar , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Peptídeo Natriurético Encefálico/metabolismo , Pandemias , Fragmentos de Peptídeos/metabolismo , Pneumonia Viral , Volume Sistólico
6.
Cochrane Database Syst Rev ; 7: CD002251, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32619039

RESUMO

BACKGROUND: Maternal hypotension is the most frequent complication of spinal anaesthesia for caesarean section. It can be associated with nausea or vomiting and may pose serious risks to the mother (unconsciousness, pulmonary aspiration) and baby (hypoxia, acidosis, neurological injury). OBJECTIVES: To assess the effects of prophylactic interventions for hypotension following spinal anaesthesia for caesarean section. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register (9 August 2016) and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials, including full texts and abstracts, comparing interventions to prevent hypotension with placebo or alternative treatment in women having spinal anaesthesia for caesarean section. We excluded studies if hypotension was not an outcome measure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study quality and extracted data from eligible studies. We report 'Summary of findings' tables using GRADE. MAIN RESULTS: We included 125 studies involving 9469 women. Interventions were to prevent maternal hypotension following spinal anaesthesia only, and we excluded any interventions considered active treatment. All the included studies reported the review's primary outcome. Across 49 comparisons, we identified three intervention groups: intravenous fluids, pharmacological interventions, and physical interventions. Authors reported no serious adverse effects with any of the interventions investigated. Most trials reported hypotension requiring intervention and Apgar score of less than 8 at five minutes as the only outcomes. None of the trials included in the comparisons we describe reported admission to neonatal intensive care unit. Crystalloid versus control (no fluids) Fewer women experienced hypotension in the crystalloid group compared with no fluids (average risk ratio (RR) 0.84, 95% confidence interval (CI) 0.72 to 0.98; 370 women; 5 studies; low-quality evidence). There was no clear difference between groups in numbers of women with nausea and vomiting (average RR 0.19, 95% CI 0.01 to 3.91; 1 study; 69 women; very low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (60 babies, low-quality evidence). Colloid versus crystalloid Fewer women experienced hypotension in the colloid group compared with the crystalloid group (average RR 0.69, 95% CI 0.58 to 0.81; 2009 women; 27 studies; very low-quality evidence). There were no clear differences between groups for maternal hypertension requiring intervention (average RR 0.64, 95% CI 0.09 to 4.46, 3 studies, 327 women; very low-quality evidence), maternal bradycardia requiring intervention (average RR 0.98, 95% CI 0.54 to 1.78, 5 studies, 413 women; very low-quality evidence), nausea and/or vomiting (average RR 0.89, 95% CI 0.66 to 1.19, 14 studies, 1058 women, I² = 29%; very low-quality evidence), neonatal acidosis (average RR 0.83, 95% CI 0.15 to 4.52, 6 studies, 678 babies; very low-quality evidence), or Apgar score of less than 8 at five minutes (average RR 0.24, 95% CI 0.03 to 2.05, 10 studies, 730 babies; very low-quality evidence). Ephedrine versus phenylephrine There were no clear differences between ephedrine and phenylephrine groups for preventing maternal hypotension (average RR 0.92, 95% CI 0.71 to 1.18; 401 women; 8 studies; very low-quality evidence) or hypertension (average RR 1.72, 95% CI 0.71 to 4.16, 2 studies, 118 women, low-quality evidence). Rates of bradycardia were lower in the ephedrine group (average RR 0.37, 95% CI 0.21 to 0.64, 5 studies, 304 women, low-quality evidence). There was no clear difference in the number of women with nausea and/or vomiting (average RR 0.76, 95% CI 0.39 to 1.49, 4 studies, 204 women, I² = 37%, very low-quality evidence), or babies with neonatal acidosis (average RR 0.89, 95% CI 0.07 to 12.00, 3 studies, 175 babies, low-quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (321 babies; low-quality evidence). Ondansetron versus control Ondansetron administration was more effective than control (placebo saline) for preventing hypotension requiring treatment (average RR 0.67, 95% CI 0.54 to 0.83; 740 women, 8 studies, low-quality evidence), bradycardia requiring treatment (average RR 0.49, 95% CI 0.28 to 0.87; 740 women, 8 studies, low-quality evidence), and nausea and/or vomiting (average RR 0.35, 95% CI 0.24 to 0.51; 653 women, 7 studies, low-quality evidence). There was no clear difference between the groups in rates of neonatal acidosis (average RR 0.48, 95% CI 0.05 to 5.09; 134 babies; 2 studies, low-quality evidence) or Apgar scores of less than 8 at five minutes (284 babies, low-quality evidence). Lower limb compression versus control Lower limb compression was more effective than control for preventing hypotension (average RR 0.61, 95% CI 0.47 to 0.78, 11 studies, 705 women, I² = 65%, very low-quality evidence). There was no clear difference between the groups in rates of bradycardia (RR 0.63, 95% CI 0.11 to 3.56, 1 study, 74 women, very low-quality evidence) or nausea and/or vomiting (average RR 0.42, 95% CI 0.14 to 1.27, 4 studies, 276 women, I² = 32%, very-low quality evidence). No baby had an Apgar score of less than 8 at five minutes in either group (130 babies, very low-quality evidence). Walking versus lying There was no clear difference between the groups for women with hypotension requiring treatment (RR 0.71, 95% CI 0.41 to 1.21, 1 study, 37 women, very low-quality evidence). Many included studies reported little to no information that would allow an assessment of their risk of bias, limiting our ability to draw meaningful conclusions. GRADE assessments of the quality of evidence ranged from very low to low. We downgraded evidence for limitations in study design, imprecision, and indirectness; most studies assessed only women scheduled for elective caesarean sections. External validity also needs consideration. Readers should question the use of colloids in this context given the serious potential side effects such as allergy and renal failure associated with their administration. AUTHORS' CONCLUSIONS: While interventions such as crystalloids, colloids, ephedrine, phenylephrine, ondansetron, or lower leg compression can reduce the incidence of hypotension, none have been shown to eliminate the need to treat maternal hypotension in some women. We cannot draw any conclusions regarding rare adverse effects associated with use of the interventions (for example colloids) due to the relatively small numbers of women studied.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/prevenção & controle , Complicações Intraoperatórias/prevenção & controle , Antieméticos/uso terapêutico , Coloides/uso terapêutico , Soluções Cristaloides/uso terapêutico , Efedrina/uso terapêutico , Feminino , Humanos , Hipotensão/induzido quimicamente , Soluções Isotônicas/uso terapêutico , Ondansetron/uso terapêutico , Fenilefrina/uso terapêutico , Náusea e Vômito Pós-Operatórios/tratamento farmacológico , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Vasoconstritores/uso terapêutico , Caminhada
7.
Toxicon ; 185: 5-14, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32569848

RESUMO

Cardiovascular effects induced by snake venoms, in spite of having a crucial role in the outcome of the envenomation, have been less studied than other toxic activities displayed by these venoms. In this study we evaluated acute cardiovascular responses to Bothrops leucurus venom - Bl-V - both in vivo, in anesthetized rats, and in vitro, in isolated rat mesenteric resistance arteries. Bl-V (10-100 µg protein/kg) caused dose-dependent hypotension, followed by gradual recovery (2-20 min) to basal levels, and induced dose-dependent (1-20 µg/mL) vasodilation in pre-contracted arteries, what was more pronounced when the endothelium remained intact. These effects were partially counteracted by pre-treatment with indomethacin (cyclooxygenase inhibitor). Prior incubation of Bl-V with commercial pentavalent Bothrops antivenom also attenuated the cardiovascular effects induced by the venom, in spite of it not being among the venoms used for the development of the bothropic antivenom. Through an approach based on two chromatographic steps and mass spectrometry (MALDI-ToF and MALDI-ISD), a component with acute cardiovascular effects was isolated and identified as the basic phospholipase blD-PLA2, previously purified from the venom of B. leucurus. Taken together, our results show that, at low doses, the venom of B. leucurus induces transient, acute hypotension in anesthetized rats following systemic vasodilation in a dose-dependent way. In addition, we provide clear evidence of the involvement of the enzymatic activity of blD-PLA2 in this cardiovascular response, acting via the production of vasodilating prostanoids.


Assuntos
Bothrops , Venenos de Crotalídeos/toxicidade , Fosfolipases A2/metabolismo , Animais , Hipotensão/induzido quimicamente , Ratos , Venenos de Serpentes
8.
Curr Opin Anaesthesiol ; 33(3): 291-298, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371631

RESUMO

PURPOSE OF REVIEW: Hypotension during cesarean section remains a frequent complication of spinal anesthesia and is associated with adverse maternal and fetal events. RECENT FINDINGS: Despite ongoing research, no single measure for sufficient treatment of spinal-induced hypotension was identified so far. Current literature discusses the efficacy of low-dose spinal anesthesia, timing and solutions for adequate fluid therapy and various vasopressor regimens. Present guidelines favor the use of phenylephrine over ephedrine because of decreased umbilical cord pH values, while norepinephrine is discussed as a probable superior alternative with regard to maternal bradycardia, although supporting data is limited. Alternative pharmacological approaches, such as 5HT3-receptor antagonists and physical methods may be taken into consideration to further improve hemodynamic stability. SUMMARY: Current evidence favors a combined approach of low-dose spinal anesthesia, adequate fluid therapy and vasopressor support to address maternal spinal-induced hypotension. As none of the available vasopressors is associated with relevantly impaired maternal and fetal outcomes, none of them should be abandoned from obstetric practice. Rapid crystalloid co-loading is of equivalent efficacy as compared with colloids and should be preferred because of a more favorable risk profile.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/induzido quimicamente , Vasoconstritores/efeitos adversos , Feminino , Humanos , Doença Iatrogênica , Gravidez , Simpatectomia
9.
Curr Opin Anaesthesiol ; 33(3): 417-422, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32324663

RESUMO

PURPOSE OF REVIEW: Although the indications for ß-blockers in the management of patients with congestive heart failure and myocardial infarction are well established, the use of ß-blockers in the perioperative setting remains controversial. RECENT FINDINGS: Since 2008 PeriOperative ISchemic Evaluation Trial, there have been numerous studies suggesting that perioperative ß-blockers are associated with adverse events such as hypotension, bradycardia, increased mortality, and stroke. SUMMARY: In this article, we review the most recent evidence to suggest an approach to perioperative ß-blocker use tailored to patient and surgical risk factors. We also review recent studies on off-label uses for perioperative ß-blockers.


Assuntos
Antagonistas Adrenérgicos beta/efeitos adversos , Anestesiologia/métodos , Doenças Cardiovasculares/induzido quimicamente , Cuidados Intraoperatórios/métodos , Complicações Pós-Operatórias/induzido quimicamente , Antagonistas Adrenérgicos beta/uso terapêutico , Bradicardia/induzido quimicamente , Humanos , Hipotensão/induzido quimicamente , Infarto do Miocárdio/induzido quimicamente , Assistência Perioperatória , Período Perioperatório , Fatores de Risco , Acidente Vascular Cerebral/induzido quimicamente
10.
Obstet Gynecol ; 135(5): 1145-1151, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32282591

RESUMO

OBJECTIVE: To compare the effect of exteriorized with in situ uterine repair on intraoperative nausea and vomiting during elective cesarean delivery under spinal anesthesia using a phenylephrine infusion. METHODS: This study was a randomized double-blinded controlled trial of 180 women undergoing elective cesarean delivery using a standardized anesthetic protocol. Patients were randomized to exteriorization (n=90) or in situ uterine repair (n=90). The spinal anesthetic, phenylephrine infusion, and blood pressure management were all standardized. The primary outcome was postdelivery intraoperative nausea and vomiting using a 4-point scale (0-3). A sample size of 80 patients per group was needed to demonstrate a 50% reduction in intraoperative nausea and vomiting with in situ repair. RESULTS: From November 2015 through July 2018, 180 patients were enrolled. Incidence of postdelivery intraoperative nausea and vomiting was 39% in the exteriorization group compared with 22% in the in situ group (P=.01). Incidence of hypotension (80% vs 50%; P<.001) and tachycardia (33% vs 17%; P=.02) was significantly higher in the exteriorization group, and more phenylephrine boluses were administered to this group (median 4 boluses [first and third quartiles 1.25-7] vs 2 [0-4]; P<.001). The duration of surgery, blood loss, and postoperative hemoglobin decline were similar between groups. CONCLUSION: In situ uterine repair for elective cesarean delivery under spinal anesthesia with a phenylephrine infusion is associated with less postdelivery intraoperative nausea and vomiting. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02587013.


Assuntos
Antieméticos/administração & dosagem , Parto Obstétrico/efeitos adversos , Histerotomia/métodos , Complicações Intraoperatórias/prevenção & controle , Fenilefrina/administração & dosagem , Adulto , Raquianestesia , Cesárea/métodos , Método Duplo-Cego , Feminino , Humanos , Hipotensão/induzido quimicamente , Hipotensão/epidemiologia , Incidência , Complicações Intraoperatórias/epidemiologia , Complicações Intraoperatórias/etiologia , Náusea/epidemiologia , Náusea/etiologia , Náusea/prevenção & controle , Gravidez , Taquicardia/induzido quimicamente , Taquicardia/epidemiologia , Resultado do Tratamento , Útero/cirurgia , Vômito/epidemiologia , Vômito/etiologia , Vômito/prevenção & controle
11.
Acta Orthop ; 91(3): 293-298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32237931

RESUMO

Background and purpose - The bone cement implantation syndrome characterized by hypotension and/or hypoxia is a well-known complication in cemented arthroplasty. We studied the incidence of hypotension and/or hypoxia in patients undergoing cemented or uncemented hemiarthroplasty for femoral neck fractures and evaluated whether bone cement was an independent risk factor for postoperative mortality.Patients and methods - In this retrospective cohort study, 1,095 patients from 2 hospitals undergoing hemiarthroplasty with (n = 986) and without (n = 109) bone cementation were included. Pre-, intra-, and postoperative data were obtained from electronic medical records. Each patient was classified for grade of hypotension and hypoxia during and after prosthesis insertion according to Donaldson's criteria (Grade 1, 2, 3). After adjustments for confounders, the hazard ratio (HR) for the use of bone cement on 1-year mortality was assessed.Results - The incidence of hypoxia and/or hypotension was higher in the cemented (28%) compared with the uncemented group (17%) (p = 0.003). The incidence of severe hypotension/hypoxia (grade 2 or 3) was 6.9% in the cemented, but not observed in the uncemented group. The use of bone cement was an independent risk factor for 1-year mortality (HR 1.9, 95% CI 1.3-2.7), when adjusted for confounders.Interpretation - The use of bone cement in hemiarthroplasty for femoral neck fractures increases the incidence of intraoperative hypoxia and/or hypotension and is an independent risk factor for postoperative 1-year mortality. Efforts should be made to identify patients at risk for BCIS and alternative strategies for the management of these patients should be considered.


Assuntos
Artroplastia de Quadril/efeitos adversos , Cimentos para Ossos/efeitos adversos , Fraturas do Colo Femoral/cirurgia , Hemiartroplastia/efeitos adversos , Hipotensão/induzido quimicamente , Hipóxia/induzido quimicamente , Complicações Intraoperatórias/induzido quimicamente , Idoso de 80 Anos ou mais , Artroplastia de Quadril/métodos , Artroplastia de Quadril/mortalidade , Cimentos para Ossos/uso terapêutico , Feminino , Fraturas do Colo Femoral/mortalidade , Hemiartroplastia/métodos , Hemiartroplastia/mortalidade , Humanos , Masculino , Estudos Retrospectivos
12.
Arterioscler Thromb Vasc Biol ; 40(5): 1207-1219, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32188278

RESUMO

OBJECTIVE: Intravenous acetaminophen/paracetamol (APAP) is well documented to cause hypotension. Since the patients receiving intravenous APAP are usually critically ill, any severe hemodynamic changes, as with those associated with APAP, can be life-threatening. The mechanism underlying this dangerous iatrogenic effect of APAP was unknown. Approach and Results: Here, we show that intravenous APAP caused transient hypotension in rats, which was attenuated by the Kv7 channel blocker, linopirdine. APAP metabolite N-acetyl-p-benzoquinone imine caused vasodilatation of rat mesenteric arteries ex vivo. This vasodilatation was sensitive to linopirdine and also the calcitonin gene-related peptide antagonist, BIBN 4096. Further investigation revealed N-acetyl-p-benzoquinone imine stimulates calcitonin gene-related peptide release from perivascular nerves, causing a cAMP-dependent activation of Kv7 channels. We also show that N-acetyl-p-benzoquinone imine enhances Kv7.4 and Kv7.5 channels overexpressed in oocytes, suggesting that it can activate Kv7.4 and Kv7.5 channels directly, to elicit vasodilatation. CONCLUSIONS: Direct and indirect activation of Kv7 channels by the APAP metabolite N-acetyl-p-benzoquinone imine decreases arterial tone, which can lead to a drop in blood pressure. Our findings provide a molecular mechanism and potential preventive intervention for the clinical phenomenon of intravenous APAP-dependent transient hypotension.


Assuntos
Acetaminofen/toxicidade , Pressão Sanguínea/efeitos dos fármacos , Hipotensão/induzido quimicamente , Canais de Potássio KCNQ/agonistas , Artérias Mesentéricas/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Acetaminofen/metabolismo , Animais , Benzoquinonas , Hipotensão/metabolismo , Hipotensão/fisiopatologia , Iminas , Canais de Potássio KCNQ/genética , Canais de Potássio KCNQ/metabolismo , Masculino , Potenciais da Membrana , Artérias Mesentéricas/metabolismo , Artérias Mesentéricas/fisiopatologia , Ratos Wistar , Transdução de Sinais , Xenopus laevis
13.
N Engl J Med ; 382(20): 1883-1893, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32222134

RESUMO

BACKGROUND: The effect of vericiguat, a novel oral soluble guanylate cyclase stimulator, in patients with heart failure and reduced ejection fraction who had recently been hospitalized or had received intravenous diuretic therapy is unclear. METHODS: In this phase 3, randomized, double-blind, placebo-controlled trial, we assigned 5050 patients with chronic heart failure (New York Heart Association class II, III, or IV) and an ejection fraction of less than 45% to receive vericiguat (target dose, 10 mg once daily) or placebo, in addition to guideline-based medical therapy. The primary outcome was a composite of death from cardiovascular causes or first hospitalization for heart failure. RESULTS: Over a median of 10.8 months, a primary-outcome event occurred in 897 of 2526 patients (35.5%) in the vericiguat group and in 972 of 2524 patients (38.5%) in the placebo group (hazard ratio, 0.90; 95% confidence interval [CI], 0.82 to 0.98; P = 0.02). A total of 691 patients (27.4%) in the vericiguat group and 747 patients (29.6%) in the placebo group were hospitalized for heart failure (hazard ratio, 0.90; 95% CI, 0.81 to 1.00). Death from cardiovascular causes occurred in 414 patients (16.4%) in the vericiguat group and in 441 patients (17.5%) in the placebo group (hazard ratio, 0.93; 95% CI, 0.81 to 1.06). The composite of death from any cause or hospitalization for heart failure occurred in 957 patients (37.9%) in the vericiguat group and in 1032 patients (40.9%) in the placebo group (hazard ratio, 0.90; 95% CI, 0.83 to 0.98; P = 0.02). Symptomatic hypotension occurred in 9.1% of the patients in the vericiguat group and in 7.9% of the patients in the placebo group (P = 0.12), and syncope occurred in 4.0% of the patients in the vericiguat group and in 3.5% of the patients in the placebo group (P = 0.30). CONCLUSIONS: Among patients with high-risk heart failure, the incidence of death from cardiovascular causes or hospitalization for heart failure was lower among those who received vericiguat than among those who received placebo. (Funded by Merck Sharp & Dohme [a subsidiary of Merck] and Bayer; VICTORIA ClinicalTrials.gov number, NCT02861534.).


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Pirimidinas/uso terapêutico , Administração Oral , Idoso , Doenças Cardiovasculares/mortalidade , Doença Crônica , Método Duplo-Cego , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Compostos Heterocíclicos com 2 Anéis/efeitos adversos , Hospitalização/estatística & dados numéricos , Humanos , Hipotensão/induzido quimicamente , Incidência , Masculino , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Guanilil Ciclase Solúvel/metabolismo , Volume Sistólico , Síncope/induzido quimicamente , Disfunção Ventricular Esquerda/tratamento farmacológico
14.
J Spec Oper Med ; 20(1): 31-33, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32203601

RESUMO

Ketamine's favorable hemodynamic and safety profile is motivating increasing use in the prehospital environment. Despite these advantages, certain side effects require advanced planning and training. We present a case of rapid intravenous administration of ketamine causing bradycardia and hypotension. A 46-year-old man presented to the emergency department for an exacerbation of chronic shoulder pain. Given the chronicity of the pain and multiple failed treatment attempts, ketamine at an analgesic dose was used. Despite the local protocol directing administration over several minutes, it was pushed rapidly, resulting in malaise, nausea, pallor, bradycardia, and hypotension. The patient returned to his baseline without intervention. This and other known side effects of ketamine, such as behavioral disturbances, altered sense of reality, and elevated heart rate and blood pressure, are well documented in the literature. With this report, the authors aim to raise awareness of transient bradycardia and hypotension associated with the rapid administration of ketamine at an analgesic dose.


Assuntos
Analgésicos/efeitos adversos , Bradicardia/induzido quimicamente , Hipotensão/induzido quimicamente , Ketamina/efeitos adversos , Analgésicos/administração & dosagem , Serviço Hospitalar de Emergência , Humanos , Infusões Intravenosas , Ketamina/administração & dosagem , Masculino , Pessoa de Meia-Idade
15.
Anaesthesia ; 75(6): 800-808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32012226

RESUMO

Phenylephrine is recommended for the management of hypotension after spinal anaesthesia in women undergoing caesarean section. Noradrenaline, an adrenergic agonist with weak ß-adrenergic activity, has been reported to have a more favourable haemodynamic profile than phenylephrine. However, there are concerns that noradrenaline may be associated with a higher risk of fetal acidosis, defined as an umbilical artery pH < 7.20. We performed a systematic review of trials comparing noradrenaline with phenylephrine, concentrating on primary outcomes of fetal acidosis and maternal hypotension. We identified 13 randomised controlled trials including 2002 patients. Heterogeneity among the studies was high, and there were too few data to calculate a pooled effect estimate. Fetal acidosis was assessed in four studies that had a low risk of bias and a low risk of confounding, that is, studies which used a prophylactic vasopressor and where women received the allocated vasopressor only. There were no significant differences between these studies. No significant differences were observed for hypotension. Two trials found a significantly lower incidence of bradycardia when using noradrenaline. Cardiac output was significantly higher after noradrenaline in two of three studies. For other secondary outcomes including nausea, vomiting and Apgar scores at 1 and 5 min, no studies found significant differences. The evidence so far is too limited to support an advantage of noradrenaline over phenylephrine. Concerns of a deleterious effect of noradrenaline on fetal blood gas status cannot currently be assuaged by the available data from randomised controlled studies.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea , Hipotensão/prevenção & controle , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Adulto , Feminino , Humanos , Hipotensão/induzido quimicamente , Gravidez , Vasoconstritores/uso terapêutico
16.
PLoS One ; 15(2): e0229736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32108177

RESUMO

OBJECTIVE: To evaluate the effects of intravenous maropitant on arterial blood pressure in healthy dogs while awake and under general anesthesia. DESIGN: Experimental crossover study. ANIMALS: Eight healthy adult Beagle dogs. PROCEDURE: All dogs received maropitant (1 mg kg-1) intravenously under the following conditions: 1) awake with non-invasive blood pressure monitoring (AwNIBP), 2) awake with invasive blood pressure monitoring (AwIBP), 3) premedication with acepromazine (0.005 mg kg-1) and butorphanol (0.2 mg kg-1) intramuscularly followed by propofol induction and isoflurane anesthesia (GaAB), and 4) premedication with dexmedetomidine (0.005 mg kg-1) and butorphanol (0.2 mg kg-1) intramuscularly followed by propofol induction and isoflurane anesthesia (GaDB). Heart rate (HR), systolic (SAP), diastolic (DAP), and mean blood pressures (MAP) were recorded before injection of maropitant (baseline), during the first 60 seconds of injection, during the second 60 seconds of injection, at the completion of injection and every 2 minutes post injection for 18 minutes. The data were compared over time using a Generalized Linear Model with mixed effects and then with simple effect comparison with Bonferroni adjustments (p <0.05). RESULTS: There were significant decreases from baseline in SAP in the GaAB group (p < 0.01) and in MAP and DAP in the AwIBP and GaAB (p < 0.001) groups during injection. A significant decrease in SAP (p < 0.05), DAP (p < 0.05), and MAP (p < 0.05) occurred at 16 minutes post injection in GaDB group. There was also a significant increase in HR in the AwIBP group (p < 0.01) during injection. Clinically significant hypotension occurred in the GaAB group with a mean MAP at 54 ± 6 mmHg during injection. CONCLUSION: Intravenous maropitant administration significantly decreases arterial blood pressure during inhalant anesthesia. Patients premedicated with acepromazine prior to isoflurane anesthesia may develop clinically significant hypotension.


Assuntos
Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Quinuclidinas/administração & dosagem , Quinuclidinas/efeitos adversos , Acepromazina/efeitos adversos , Anestesia por Inalação/veterinária , Animais , Doenças do Cão/induzido quimicamente , Doenças do Cão/fisiopatologia , Cães , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipotensão/induzido quimicamente , Hipotensão/fisiopatologia , Hipotensão/veterinária , Injeções Intravenosas/veterinária , Modelos Lineares , Modelos Animais , Pré-Medicação/efeitos adversos , Pré-Medicação/veterinária , Vigília
17.
BMJ Case Rep ; 13(1)2020 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-32014989

RESUMO

We present a case of a young Asian female with rheumatoid arthritis who received latent tuberculosis infection (LTBI) treatment prior to treatment with a biologic agent, and developed shock with resistant hypotension on re-exposure to rifampicin. We discuss the epidemiology, pathophysiology and management of rifampicin induced shock, concluding that clinicians should be aware of this rare, but potential adverse effect, and be aware that adverse reactions to rifampicin are more frequent during re-exposure or longer dosing interval regimes. The evidence for desensitisation following such a reaction is lacking and this approach is not currently recommended. We would suggest close collaboration between specialties prescribing immunosuppression and the tuberculosis team when LTBI treatment is required after a reaction, with patient involvement to discuss the risks and benefits of treatment options.


Assuntos
Antituberculosos/efeitos adversos , Hipotensão/induzido quimicamente , Tuberculose Latente/tratamento farmacológico , Rifampina/efeitos adversos , Choque Séptico/induzido quimicamente , Adulto , Feminino , Hidratação , Humanos , Hipotensão/diagnóstico , Hipotensão/terapia , Retratamento , Choque Séptico/diagnóstico , Choque Séptico/tratamento farmacológico
18.
BMC Pharmacol Toxicol ; 21(1): 5, 2020 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-31918741

RESUMO

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors inhibit SGLT2, which is expressed in the proximal renal tubule, and thus reduce blood glucose levels by enabling the urinary excretion of excess glucose. SGLT2 inhibitors have been reported to suppress the complications of diabetes and reduce overall mortality. However, little is known about the types of symptoms that may occur in response to an overdose of an SGLT2 inhibitor. Here, we describe a case of intoxication caused by an overdose of an SGLT2 inhibitor. CASE PRESENTATION: An otherwise physically healthy adult woman ingested an overdose of ipragliflozin, an SGLT2 inhibitor, and a polypill of olmesartan medoxomil, and azelnidipine in a suicide attempt. Although her blood ipragliflozin concentration was very high (9516.3 ng/mL) upon hospital arrival, her initial blood glucose level was normal, and she did not exhibit symptoms such as hypoglycemia or polyuria. Moderate renal dysfunction associated with an estimated glomerular filtration rate of 42.3 mL/min/1.73 m2 was observed. Thirty-six hours after ingestion, her blood ipragliflozin concentration decreased to a level equivalent to that observed after a therapeutic dose and her renal function improved almost simultaneously. After improvement in her renal function, the osmotic diuretic effect of the drug progressed. Her blood glucose level declined slightly but was in the normal range due to glucose administration. During the clinical course, fatal hypoglycemia was not observed. CONCLUSIONS: Our case showed that an overdose of an SGLT2 inhibitor caused toxic effects on renal function, but severe hypoglycemia was not observed. Additional cases of intoxication from SGLT2 inhibitors alone would be helpful to clarify the mechanism of intoxication.


Assuntos
Glucosídeos/toxicidade , Inibidores do Transportador 2 de Sódio-Glicose/toxicidade , Tiofenos/toxicidade , Adulto , Overdose de Drogas , Feminino , Humanos , Hipotensão/induzido quimicamente , Rim/efeitos dos fármacos , Rim/fisiopatologia
20.
Arch Dis Child Fetal Neonatal Ed ; 105(5): 489-495, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31932363

RESUMO

OBJECTIVE: To find propofol doses providing effective sedation without side effects in neonates of different gestational ages (GA) and postnatal ages (PNA). DESIGN AND SETTING: Prospective multicentere dose-finding study in 3 neonatal intensive care units. PATIENTS: Neonates with a PNA <28 days requiring non-emergency endotracheal intubation. INTERVENTIONS: Neonates were stratified into 8 groups based on GA and PNA. The first 5 neonates in every group received a dose of 1.0 mg/kg propofol. Based on sedative effect and side effects, the dose was increased or decreased in the next 5 patients until the optimal dose was found. MAIN OUTCOME MEASURES: The primary outcome was the optimal single propofol starting dose that provides effective sedation without side effects in each age group. RESULTS: After inclusion of 91 patients, the study was prematurely terminated because the primary outcome was only reached in 13% of patients. Dose-finding was completed in 2 groups, but no optimal propofol dose was found. Effective sedation without side effects was achieved more often after a starting dose of 2.0 mg/kg (28%) than after 1.0 mg/kg (3%) and 1.5 mg/kg (9%). Propofol-induced hypotension occurred in 59% of patients. Logistic regression analyses showed that GA and PNA did not predict effective sedation or the occurrence of hypotension. CONCLUSIONS: Effective sedation without side effects is difficult to achieve with propofol and the optimal dose in different age groups of neonates could not be determined. The sedative effect of propofol and the occurrence of hypotension are unpredictable and show large inter-individual variability in the neonatal population.


Assuntos
Hipnóticos e Sedativos/administração & dosagem , Intubação Intratraqueal/métodos , Propofol/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Humanos , Hipnóticos e Sedativos/efeitos adversos , Hipotensão/induzido quimicamente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Propofol/efeitos adversos , Estudos Prospectivos
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