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1.
J Neurotrauma ; 39(1-2): 181-195, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33626966

RESUMO

Traumatic brain injury (TBI) represents a critical public health problem around the world. To date, there are no accurate therapeutic approaches for the management of cardiovascular impairments induce by TBI. In this regard, hydrogen sulfide (H2S), a novel gasotransmitter, has been proposed as a neuro- and cardioprotective molecule. This study was designed to determine the effect of subchronic management with sodium hydrosulfide (NaHS) on hemodynamic, vasopressor sympathetic outflow and sensorimotor alterations produced by TBI. Animals underwent a lateral fluid percussion injury, and changes in hemodynamic variables were measured by pletismographic methods. In addition, vasopressor sympathetic outflow was assessed by a pithed rat model. Last, sensorimotor impairments were evaluated by neuroscore test and beam-walking test. At seven, 14, 21, and 28 days after moderate-severe TBI, the animals showed: (1) a decrease on sensorimotor function in the neuroscore test and beam-walking test; (2) an increase in heart rate, systolic, diastolic, and mean blood pressure; (3) progressive sympathetic hyperactivity; and (4) a decrease in vasopressor responses induced by noradrenaline (α1/2-adrenoceptors agonist) and UK 14,304 (selective α2-adrenoceptor agonist). Interestingly, intraperitoneal daily injections of NaHS, an H2S donor (3.1 and 5.6 mg/kg), during seven days after TBI prevented the development of the impairments in hemodynamic variables, which were similar to those obtained in sham animals. Moreover, NaHS treatment prevented the sympathetic hyperactivity and decreased noradrenaline-induced vasopressor responses. No effects on sensorimotor dysfunction were observed, however. Taken together, our results suggest that H2S ameliorates the hemodynamic and sympathetic system impairments observed after TBI.


Assuntos
Lesões Encefálicas Traumáticas , Sulfeto de Hidrogênio , Hipertensão , Animais , Lesões Encefálicas Traumáticas/complicações , Sulfeto de Hidrogênio/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/farmacologia
2.
Crit Care ; 26(1): 231, 2022 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-35909163

RESUMO

BACKGROUND: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. METHODS: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. RESULTS: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78-1.39] in the no-, 1.22 [98.3% CI 0.97-1.53] in the moderate-, and 0.97 [98.3% CI 0.68-1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. CONCLUSIONS: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308 , registered September 20, 2016.


Assuntos
Reanimação Cardiopulmonar , Hipotermia Induzida , Parada Cardíaca Extra-Hospitalar , Adulto , Reanimação Cardiopulmonar/métodos , Epinefrina/uso terapêutico , Humanos , Hipotermia Induzida/métodos , Norepinefrina/uso terapêutico , Parada Cardíaca Extra-Hospitalar/tratamento farmacológico , Temperatura , Vasoconstritores/uso terapêutico
3.
Curr Opin Crit Care ; 28(4): 419-425, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35792520

RESUMO

PURPOSE OF REVIEW: Despite increasing interest in the management of cardiogenic shock (CS), mortality rates remain unacceptably high. The mainstay of supportive treatment includes vasopressors and inotropes. These medications are recommended in international guidelines and are widely used despite limited evidence supporting safety and efficacy in CS. RECENT FINDINGS: The OptimaCC trial further supports that norepinephrine should continue to be the first-line vasopressor of choice in CS. The CAPITAL DOREMI trial found that milrinone is not superior to dobutamine in reducing morbidity and mortality in CS. Two studies currently underway will offer the first evidence of the necessity of inotrope therapy in placebo-controlled trials: CAPITAL DOREMI2 will randomize CS patients to inotrope or placebo in the initial resuscitation of shock to evaluate the efficacy of inotrope therapy and LevoHeartShock will examine the efficacy of levosimendan against placebo in early CS requiring vasopressor therapy. SUMMARY: Review of the current literature fails to show significant mortality benefit with any specific vasopressor or inotropic in CS patients. The upcoming DOREMI 2 and levosimendan versus placebo trials will further tackle the question of inotrope necessity in CS. At this time, inotrope selection should be guided by physician experience, availability, cost, and most importantly, individual patients' response to therapy.


Assuntos
Cardiotônicos , Choque Cardiogênico , Cardiotônicos/uso terapêutico , Dobutamina/uso terapêutico , Humanos , Choque Cardiogênico/tratamento farmacológico , Simendana/uso terapêutico , Vasoconstritores/uso terapêutico
4.
Sci Rep ; 12(1): 12829, 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35896794

RESUMO

This study was performed to elucidate whether eicosapentaenoic acid (EPA) suppresses spasm-prone blood vessel contractions induced by a thromboxane mimetic (U46619) and prostaglandin F2α (PGF2α) and determine whether the primary target of EPA is the prostanoid TP receptor. Accordingly, we assessed: (1) the tension changes in porcine basilar and coronary arteries, and (2) changes in the Fura-2 (an intracellular Ca2+ indicator) fluorescence intensity ratio at 510 nm elicited by 340/380 nm excitation (F340/380) in 293T cells expressing the human TP receptor (TP-293T cells) and those expressing the human prostanoid FP receptor (FP-293T cells). EPA inhibited both porcine basilar and coronary artery contractions induced by U46619 and PGF2α in a concentration-dependent manner, but it did not affect the contractions induced by 80 mM KCl. EPA also inhibited the increase in F340/380 induced by U46619 and PGF2α in TP-293T cells. In contrast, EPA showed only a marginal effect on the increase in F340/380 induced by PGF2α in FP-293T cells. These findings indicate that EPA strongly suppresses the porcine basilar and coronary artery contractions mediated by TP receptor and that inhibition of TP receptors partly underlies the EPA-induced inhibitory effects on these arterial contractions.


Assuntos
Ácido Eicosapentaenoico , Vasoconstritores , Ácido 15-Hidroxi-11 alfa,9 alfa-(epoximetano)prosta-5,13-dienoico/farmacologia , Animais , Artérias Cerebrais , Dinoprosta/farmacologia , Ácido Eicosapentaenoico/farmacologia , Humanos , Receptores de Prostaglandina , Receptores de Tromboxano A2 e Prostaglandina H2/fisiologia , Suínos , Vasoconstritores/farmacologia
5.
Anaesthesiol Intensive Ther ; 54(2): 141-149, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35792110

RESUMO

INTRODUCTION: Vasopressors increase arterial pressure but they may have deleterious effects on mesenteric blood flow. We aimed to evaluate the response of gut biomarkers and superior mesenteric blood flow to different vasopressors with and without dobutamine. MATERIAL AND METHODS: Thirty New Zealand rabbits were included and randomly allocated to 5 groups: group A - sham group; group B - norepinephrine; group C - norepinephrine plus dobutamine; group D - vasopressin; and group E - vasopressin plus dobutamine. Mean arterial pressure (MAP) target was greater than 60 mmHg. Endotoxic shock was induced by intra-venous injection of lipopolysaccharide (LPS) in four of the five groups. Aortic blood flow (Qao), superior mesenteric artery flow (QSMA) and lactate were measured after LPS injection. Enterocyte damage was evaluated by measurements of serum citrulline and intestinal fatty acid-binding protein (I-FABP) after 4 h. RESULTS: The largest reduction in Qao occurred in group D (64 ± 17.3 to 38 ± 7.5 mL min-1; P = 0.04). QSMA also declined significantly in groups D and E and remained lower than in the other groups over 4 h (group D - baseline: 65 ± 31; 1 h: 37 ± 10; 2 h: 38 ± 10; 3 h: 46 ± 26; and 4 h: 48 ± 15 mL min-1; P < 0.005; group E - baseline: 73 ± 14; 1 h: 28 ± 4.0; 2 h: 37 ± 6.4; 3 h: 40 ± 11; and 4 h: 48 ± 11; P < 0.005; all in mL min-1). Serum citrulline was significantly lower in groups D (P = 0.014) and E (P = 0.019) in comparison to group A. The fluid administration regimen was similar in all groups. CONCLUSIONS: Vasopressin seems to negatively impact gut enterocyte function during endotoxic shock despite the association of an inodilator and adequate fluid replacement.


Assuntos
Dobutamina , Choque Séptico , Animais , Citrulina , Dobutamina/farmacologia , Dobutamina/uso terapêutico , Hemodinâmica , Humanos , Lipopolissacarídeos/farmacologia , Norepinefrina/farmacologia , Coelhos , Choque Séptico/tratamento farmacológico , Vasoconstritores/farmacologia , Vasopressinas/farmacologia
6.
Arq Gastroenterol ; 59(2): 268-274, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35830040

RESUMO

BACKGROUND: Hepatorenal syndrome (HRS) is the most severe form of acute kidney injury in patients with advanced cirrhosis, and it is associated with high mortality. It is usually diagnosed according to criteria defined by the International Ascites Club. Currently, the most frequently indicated pharmacological therapy for the treatment of HRS is a combination of splanchnic vasoconstrictors (terlipressin or norepinephrine) in combination with albumin. With the progressive increase in healthcare spending, it is important to conduct a cost-effectiveness analysis of pharmacological treatment in patients who are diagnosed with HRS. OBJECTIVE: To perform a cost-effectiveness assessment for the use of terlipressin in combination with albumin to treat HRS in patients with cirrhosis. METHODS: Economic evaluation of cost-effectiveness based on secondary data from studies showed the efficacy of terlipressin therapy compared with norepinephrine combined with albumin or albumin alone. The cost-effectiveness analysis was calculated using an incremental cost-effectiveness ratio (ICER), and a sensitivity analysis was developed by varying the values of therapies and probabilities. The Brazilian real was the currency used in the analysis, and the results were converted to US dollars. RESULTS: After selection, eligibility, and evaluation of the quality of publications, the results demonstrated that administration of terlipressin or norepinephrine in combination with albumin in patients diagnosed with HRS type 1 was efficacious. The cost of treatment with terlipressin in combination with albumin was USD $1,644.06, administration of albumin alone was USD $912.02, and norepinephrine plus albumin was USD $2,310.78. Considering that the combination therapies demonstrated effectiveness, the incremental cost of terlipressin and norepinephrine in combination with albumin was USD $666.73, and an effectiveness of 0.570 was found for terlipressin in combination with albumin and 0.200 for norepinephrine in combination with albumin. The incremental effectiveness was 0.370, and the ICER was USD $1,801.97. Thus, the parameters of increasing cost per therapy and ICER indicated that the combined therapy of terlipressin plus albumin was cost effective compared to albumin alone or norepinephrine plus albumin in a public single-payer healthcare system. CONCLUSION: A cost-effectiveness analysis showed that terlipressin in combination with albumin when administered concomitantly to patients who were diagnosed with type 1 HRS is cost-effective compared to norepinephrine in combination with albumin administered in a controlled environment.


Assuntos
Síndrome Hepatorrenal , Albuminas/uso terapêutico , Análise Custo-Benefício , Quimioterapia Combinada , Síndrome Hepatorrenal/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Lipressina/uso terapêutico , Norepinefrina/uso terapêutico , Terlipressina/uso terapêutico , Resultado do Tratamento , Vasoconstritores/uso terapêutico
7.
Drug Des Devel Ther ; 16: 2189-2198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837022

RESUMO

Background: It is well-known that severe preeclamptic parturients have less vasopressor requirements than normotensive parturients; however, the exact dose difference is poorly documented. This study aimed to determine and compare the ED50 and ED90 of a single bolus phenylephrine for the treatment of spinal anesthesia-induced hypotension in parturients with severe preeclampsia and parturients with normotension. Methods: Seventy-five parturients with severe preeclampsia scheduled for cesarean delivery under combined spinal-epidural anesthesia were enrolled and randomly allocated to receive a single bolus of phenylephrine at five different doses (40, 50, 60, 70, and 80 µg), whereas 75 parturients with normotension were randomized to receive a single bolus of phenylephrine at five different doses (70, 80, 90, 100, and 110 µg) for the treatment of the first episode of hypotension. Phenylephrine dose values were log-transformed, the proportions of the successful interventions at each dose were converted to probits, and regression analysis was performed. Results: The ED50 and ED90 (95% CI) of bolus phenylephrine were 72.1 (61.7 to 79.9) µg and 107 (95.9-128.6) µg in parturients with normotension. The ED50 and ED90 values in parturients with severe preeclampsia were 47.6 (41.3-52.7) µg and 70.7 (62.9-86.7) µg. The relative median potency was 1.51 (1.16-2.61). Conclusion: Under this study conditions, severe preeclamptic parturients required a 34% reduction of ED50 of phenylephrine dose compared with normotensive parturients.


Assuntos
Raquianestesia , Hipotensão Controlada , Hipotensão , Pré-Eclâmpsia , Raquianestesia/efeitos adversos , Cesárea , Método Duplo-Cego , Feminino , Humanos , Hipotensão/induzido quimicamente , Hipotensão/tratamento farmacológico , Fenilefrina/efeitos adversos , Pré-Eclâmpsia/tratamento farmacológico , Gravidez , Vasoconstritores/efeitos adversos
8.
Methods Mol Biol ; 2515: 75-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35776346

RESUMO

The endothelin-1 (ET-1) model of stroke involves the stereotactic injection of the vasoconstrictor ET-1 to produce a focal ischemic injury. In rats, this model produces consistent deficits, in contrast to more variable results in mice. In this chapter, we describe a new method to induce a murine focal ischemic cortical stroke by injecting L-NAME, another potent vasoconstrictor , in combination with ET-1 into the sensorimotor cortex. This ET-1 /L-NAME stroke induction protocol produces consistent focal cortical infarcts and sensorimotor functional impairments in C57BL/6 mice.


Assuntos
Endotelina-1 , Acidente Vascular Cerebral , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , NG-Nitroarginina Metil Éster/farmacologia , Ratos , Acidente Vascular Cerebral/induzido quimicamente , Vasoconstritores
9.
J Am Heart Assoc ; 11(15): e026426, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35876413

RESUMO

Background A single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion. Methods and Results Spontaneously hypertensive rats on a low-salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α-adrenergic agonist midodrine (4 mg/kg per day), or a high-salt diet (all groups n=6-7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA-mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA-treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA-treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin. Conclusions Intact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure-lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.


Assuntos
Hipertensão , Midodrina , Angiotensina II/farmacologia , Angiotensinogênio/genética , Angiotensinogênio/metabolismo , Animais , Pressão Sanguínea/fisiologia , Fludrocortisona , Hipertensão/tratamento farmacológico , Hipertensão/terapia , Camundongos , Norepinefrina , RNA Interferente Pequeno/farmacologia , Ratos , Renina/genética , Sistema Renina-Angiotensina , Vasoconstritores/farmacologia , Vasoconstritores/uso terapêutico
11.
Shock ; 57(6): 172-179, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35759300

RESUMO

ABSTRACT: Sepsis and septic shock usually show a high mortality rate and frequently need of intensive care unit admissions. After fluid resuscitation, norepinephrine (NE) is the first-choice vasopressor in septic shock patients. However, high-NE doses are associated with increased rates of adverse effects and mortality. In this perspective, many authors have proposed the administration of non-adrenergic vasopressors (NAV). Selepressin is a selective vasopressin type 1A (V1A) receptor agonist and may be a valid option in this field, because it can decrease NE requirements and also limit the deleterious effects induced by high doses of catecholamines. Only few clinical data actually support selepressin administration in this setting. Here, we review the current literature on this topic analyzing some pathophysiological aspects, the rationale about the use of NAV, the possible use of selepressin differentiating animal, and human studies. Various issues remain unresolved and future trials should be focused on early interventions based on a multimodal activation of the vasopressive pathways using both alpha and V1A receptors pathways.


Assuntos
Sepse , Choque Séptico , Catecolaminas/uso terapêutico , Humanos , Norepinefrina/uso terapêutico , Sepse/complicações , Choque Séptico/complicações , Vasoconstritores/uso terapêutico
12.
Best Pract Res Clin Anaesthesiol ; 36(1): 69-82, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35659961

RESUMO

Spinal hypotension during caesarean section remains a common complication, with important attendant maternal and fetal adverse outcomes. Research elucidating the mechanisms of spinal hypotension has led to the development and refinement of effective management strategies, with a particular emphasis on prophylactic vasopressor administration. This has proved effective in well-resourced settings, with maternal comfort and the elimination of nausea now considered the primary aim of treatment. In resource-limited settings, sophisticated strategies are not feasible due to insufficient equipment, staff, and expertise. Therefore, in these areas spinal hypotension remains an important cause of maternal and fetal morbidity and mortality. Translational, context-sensitive research in resource-limited settings has shown promise in implementing pragmatic strategies based on research from resource-rich environments. We review the current best practice for the prevention and treatment of spinal hypotension, with a special emphasis on effective strategies in resource-limited settings. We further suggest a research agenda to address the knowledge gap in specific contexts.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão , Obstetrícia , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Feminino , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/prevenção & controle , Fenilefrina , Gravidez , Vasoconstritores/uso terapêutico
13.
N Engl J Med ; 386(25): 2387-2398, 2022 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-35704292

RESUMO

BACKGROUND: Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction. METHODS: In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28. RESULTS: A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P = 0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event. CONCLUSIONS: In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274.).


Assuntos
Ácido Ascórbico , Sepse , Adulto , Ácido Ascórbico/efeitos adversos , Humanos , Hipoglicemiantes/uso terapêutico , Unidades de Terapia Intensiva , Insuficiência de Múltiplos Órgãos , Qualidade de Vida , Sepse/tratamento farmacológico , Vasoconstritores/efeitos adversos , Vitaminas/efeitos adversos
15.
West J Emerg Med ; 23(3): 358-367, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35679499

RESUMO

INTRODUCTION: Blood pressure (BP) monitoring is an essential component of sepsis management. The Surviving Sepsis Guidelines recommend invasive arterial BP (IABP) monitoring, although the benefits over non-invasive BP (NIBP) monitoring are unclear. This study investigated discrepancies between IABP and NIBP measurement and their clinical significance. We hypothesized that IABP monitoring would be associated with changes in management among patients with sepsis requiring vasopressors. METHODS: We performed a retrospective study of adult patients admitted to the critical care resuscitation unit at a quaternary medical center between January 1-December 31, 2017. We included patients with sepsis conditions AND IABP monitoring. We defined a clinically significant BP discrepancy (BPD) between NIBP and IABP measurement as a difference of > 10 millimeters of mercury (mm Hg) AND change of BP management to maintain mean arterial pressure ≥ 65 mm Hg. RESULTS: We analyzed 127 patients. Among 57 (45%) requiring vasopressors, 9 (16%) patients had a clinically significant BPD vs 2 patients (3% odds ratio [OR] 6.4; 95% CI: 1.2-30; P = 0.01) without vasopressors. In multivariable logistic regression, higher Sequential Organ Failure Assessment (SOFA) score (OR 1.33; 95% CI: 1.02-1.73; P = 0.03) and serum lactate (OR 1.27; 95% CI: 1.003-1.60, P = 0.04) were associated with increased likelihood of clinically significant BPD. There were no complications (95% CI: 0-0.02) from arterial catheter insertions. CONCLUSION: Among our population of septic patients, the use of vasopressors was associated with increased odds of a clinically significant blood pressure discrepancy between IABP and NIBP measurement. Additionally, higher SOFA score and serum lactate were associated with higher likelihood of clinically significant blood pressure discrepancy. Further studies are needed to confirm our observations and investigate the benefits vs the risk of harm of IABP monitoring in patients with sepsis.


Assuntos
Determinação da Pressão Arterial , Sepse , Adulto , Pressão Sanguínea , Humanos , Lactatos , Estudos Retrospectivos , Sepse/diagnóstico , Vasoconstritores/uso terapêutico
16.
JAMA ; 328(3): 270-279, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35707974

RESUMO

Importance: Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain. Objective: To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death. Design, Setting, and Participants: This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021. Interventions: Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527). Main Outcomes and Measures: The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge. Results: Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, -2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, -1.8% [95% CI, -7.9% to 4.3%]; P = .55). Conclusions and Relevance: Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse. Trial Registration: ClinicalTrials.gov Identifier: NCT03787732.


Assuntos
Estado Terminal , Hidratação , Parada Cardíaca , Hipotensão , Intubação Intratraqueal , Choque , Adulto , Idoso , Estado Terminal/terapia , Feminino , Parada Cardíaca/etiologia , Parada Cardíaca/mortalidade , Parada Cardíaca/terapia , Humanos , Hipnóticos e Sedativos/uso terapêutico , Hipotensão/tratamento farmacológico , Hipotensão/etiologia , Hipotensão/prevenção & controle , Intubação Intratraqueal/efeitos adversos , Masculino , Pessoa de Meia-Idade , Respiração com Pressão Positiva , Choque/etiologia , Choque/terapia , Vasoconstritores/uso terapêutico
17.
Sleep Med ; 97: 73-81, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35728308

RESUMO

INTRODUCTION: Obstructive sleep apnea (OSA) increases sympathetic vasoconstrictor drive and reduces baroreflex sensitivity (BRS), the degree to which blood pressure changes modify cardiac output. Whether nighttime continuous positive airway pressure (CPAP) corrects BRS in the awake state in OSA remains unclear. We assessed spontaneous BRS using non-invasive continuous BP and ECG recordings at rest and during handgrip and Valsalva challenges, maneuvers that increase vasoconstrictor drive with progressively higher BP, in untreated OSA (unOSA), CPAP-treated OSA (cpOSA) and healthy (CON) participants. METHODS: In a cross-sectional study of 104 participants, 34 unOSA (age mean±std, 50.6±14.1years; Respiratory Event Index [REI] 21.0±15.3 events/hour; 22male), 31 cpOSA (49.6±14.5years; REI 23.0±14.2 events/hour; 22male; self-report 4+hours/night,5+days/week,6months), and 39 CON (42.2±15.0years; 17male), we calculated BRS at rest and during handgrip and Valsalva. Additionally, we correlated BP variability (BPV) with BRS during these protocols. RESULTS: BRS in unOSA, cpOSA and CON was, respectively (mean±sdv in ms/mmHg), at rest: 14.8±11.8, 15.8±17.0, 16.1±11.3; during handgrip 13.3±7.6, 12.7±8.4, 16.4±8.7; and during Valsalva 12.7±8.0, 11.5±6.6, 15.1±8.9. BRS was lower in cpOSA than CON for handgrip (p=0.04) and Valsalva (p=0.03). BRS was negatively correlated with BPV in unOSA during Valsalva and handgrip for cpOSA, both R=-0.4 (p=0.02). BRS was negatively correlated with OSA severity (levels: none, mild, moderate, severe) at R=-0.2 (p=0.04,n=104). CONCLUSIONS: As expected, BRS was lower and BPV higher in OSA during the pressor challenges, and disease severity negatively correlated with BRS. In this cross-sectional study, both CPAP-treated (self-reported) and untreated OSA showed reduced BRS, leaving open whether within-person CPAP improves BRS.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Apneia Obstrutiva do Sono , Adulto , Barorreflexo/fisiologia , Pressão Sanguínea/fisiologia , Pressão Positiva Contínua nas Vias Aéreas/métodos , Estudos Transversais , Força da Mão , Humanos , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/terapia , Vasoconstritores
18.
Curr Med Res Opin ; 38(8): 1467-1472, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35686858

RESUMO

OBJECTIVE: The aim of this study was to examine the relationship between maternal obesity and fetal umbilical arterial pH in a cohort of parturients that received a prophylactic phenylephrine infusion for management of spinal anesthesia induced hypotension during cesarean delivery. METHODS: This was a retrospective cohort study of cesarean deliveries at a single academic tertiary care institution between January 2012 and March 2019. All scheduled nonlaboring cesarean deliveries of singleton live neonate performed under spinal anesthesia between 37 and 41 weeks gestational age were included. The primary outcome was umbilical arterial pH. Multiple regression models were used to test the relationship between umbilical arterial pH, and maternal body mass index (BMI), race, dose of phenylephrine, baseline systolic blood pressure, maximum decrease in systolic blood pressure, induction of anesthesia to delivery time and uterine incision to delivery time. RESULTS: Seven hundred and sixty-one mother neonate pairs were included in the study. The univariate analysis showed a decrease in mean umbilical arterial pH with increasing maternal BMI (p = <.01). A multivariate regression model indicated that maximum decrease in systolic blood pressure, induction of anesthesia to delivery time, and uterine incision to delivery time accounted for 11% of the variance in the outcome, R2 = 0.11. BMI was not a significant predictor of low umbilical arterial pH (p = .36). The significant predictors of low umbilical arterial pH in the model were maximum decrease in systolic blood pressure (p < .001), induction of anesthesia to delivery time (p = .04), and uterine incision to delivery time (p < .001). CONCLUSIONS: Maternal BMI is not associated with lower umbilical arterial pH in women having scheduled cesarean delivery under spinal anesthesia. Severity of spinal anesthesia induced hypotension is greater with increasing BMI and may be responsible for the observed decrease in umbilical arterial pH.


Assuntos
Anestesia Obstétrica , Raquianestesia , Hipotensão , Obesidade Materna , Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Feminino , Humanos , Concentração de Íons de Hidrogênio , Recém-Nascido , Fenilefrina , Gravidez , Estudos Retrospectivos , Vasoconstritores
19.
J Cardiothorac Vasc Anesth ; 36(9): 3543-3550, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35697643

RESUMO

OBJECTIVES: To compare the hemodynamic response of methylene blue dosing regimens (bolus v bolus plus infusion) for the treatment of vasoplegia. DESIGN: A retrospective cohort analysis. SETTING: A single-center academic medical center. PARTICIPANTS: Patients who underwent cardiac surgery at Cleveland Clinic and received methylene blue between 2016 and 2019. Patients were excluded from the analysis if methylene blue was initiated >48 hours after surgery, if the cardiac index was <2.0 L/min/m2, or if they returned to the operating room for postoperative hemorrhage. INTERVENTIONS: Methylene blue bolus-only regimens versus bolus plus continuous infusion methylene blue regimens. MEASUREMENTS AND MAIN RESULTS: The primary outcome was vasopressor requirement over 48 hours (1, 3, 6, 12, 24, and 48 hours) after methylene blue initiation. Other hemodynamic outcomes evaluated included the rate of methylene blue response, mean arterial pressure (MAP), and systemic vascular resistance (SVR) values over time. In total, 44 patients were included in the analysis, 33 of whom only received a methylene blue bolus. Vasopressor requirements at baseline were 95 (95% CI: 70-122) µg/min norepinephrine equivalent (NE) in the bolus-only group and 100 (86-130) µg/min in the infusion group. Vasopressor requirements decreased at each time point in both groups and were similar throughout (hour 1 mean [95% CI] NE, bolus 79 [67-91] µg/min v bolus plus infusion 84 [63-104] µg/min; p = 0.71). MAP, SVR, and rates of methylene blue response were similar between groups at all time points. Clinical outcomes also were similar between groups. CONCLUSIONS: The addition of a methylene blue continuous infusion did not significantly improve hemodynamic response. Bolus-only dosing of methylene blue may be sufficient for the treatment of vasoplegia after cardiac surgery.


Assuntos
Vasoplegia , Hemodinâmica , Humanos , Azul de Metileno , Norepinefrina , Estudos Retrospectivos , Vasoconstritores , Vasoplegia/tratamento farmacológico
20.
J Spec Oper Med ; 22(2): 63-68, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35639896

RESUMO

Shock is a life-threatening condition carrying a high mortality rate when untreated. The consequences of shock are cellular and metabolic derangements, which are initially reversible. The authors present the case of a Servicemember who sustained mortar shrapnel wounds that resulted in shock.


Assuntos
Choque , Vasoconstritores , Humanos , Choque/etiologia , Vasoconstritores/uso terapêutico
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