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Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

ABSTRACT: PURPOSE:(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure. METHODS:We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infusions of SNP in pediatric patients <17 years, who required controlled hypotension for at least 2 h while undergoing a surgical or medical procedure. A blinded SNP dose of 0.3, 1, 2, or 3 ?g/kg/min was infused for 30 min, followed by open-label administration for at least 90 min. Both infusions were titrated to effect. RESULTS:The final intent-to-treat group comprised 203 patients. Significant reductions in mean arterial pressure (MAP) from baseline were observed for all four doses at 20 and 25 min after the start of infusion (p ? 0.009 and p ? 0.010 for each time, respectively). Overall, 98.5% of the patients achieved the target MAP; 72.9% first achieved the target MAP during the blinded infusion. The mean infusion rate at target MAP was 1.07 ?g/kg/min. CONCLUSION:We determined that 0.3 ?g/kg/m is a reasonable starting dose for SNP in pediatric patients requiring controlled hypotension. The infusion rate can then be increased to achieve the desired reduction in blood pressure. On the basis of our results, we found an average infusion rate of 1 ?g/kg/min might be appropriate. Of note, no cyanide toxicity was reported, and no measureable cyanide levels were detected in any blood samples obtained during the study. http://clinicaltrials.gov/show/NCT00135668.

SUBMITTER: Drover DR

PROVIDER: S-EPMC4491614 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

Drover David R DR Hammer Gregory B GB Barrett Jeffrey S JS Cohane Carol A CA Reece Tammy T Zajicek Anne A Schulman Scott R SR

Frontiers in pharmacology 20150706

<h4>Purpose</h4>(1) To define the onset and offset of the blood-pressure-lowering effects of sodium nitroprusside (SNP) for use in developing instructions for dose titration in children undergoing a surgical or medical procedure, and (2) to assess the safety of SNP administration in pediatric patients requiring controlled reduction of blood pressure.<h4>Methods</h4>We conducted a randomized, double-blind, parallel-group, dose-ranging, effect-controlled, multicenter study of intravenous (IV) infu ...[more]

PMID: 26217225

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Project description:BackgroundSodium nitroprusside (SNP) is a potent vasodilator that has been used to induce deliberate hypotension in children during surgery involving significant blood loss, including craniofacial and spinal fusion procedures. SNP metabolism liberates cyanide, which may cause interference with cellular energy metabolism, leading to metabolic acidosis and central nervous system injury. We performed a retrospective, case-control study to determine whether the short-term intra-operative use of SNP for deliberate hypotension is associated with metabolic acidosis in children undergoing surgical procedures for craniofacial or spinal anomalies. Cyanide and thiocyanate concentrations were also recorded in patients who received SNP.MethodsData from 166 children undergoing craniofacial and spinal fusion surgery between 2005 and 2010 at Lucile Packard Children's Hospital (LPCH) at Stanford were analyzed. Records from 60 patients who received SNP (SNP group) as part of a multicenter, randomized, double-blind study were compared with records from 106 eligible patients who had blood pressure reduction using anesthetic agents and did not receive SNP (control group). Metabolic acidosis was defined as serum bicarbonate (HCO3) < 18.5 mEq/L. Whole blood CN, plasma thiocyanate and urinary thiocyanate concentrations were measured in patients in the SNP group. Differences in metabolic acidosis rates between the SNP and control groups were assessed through a test of noninferiority in the rate for the SNP group with a noninferiority threshold of 0.2. A z-test was used to test the null hypothesis. The alternative hypothesis was that the difference in these rates was less than 0.2. The same noninferiority threshold of 0.2 was also used to perform separate, secondary tests for noninferiority in the proportion of patients with HCO3 levels below 18.5 mEq/L and the proportion of patients who required HCO3 administration.ResultsFewer patients in the SNP group experienced metabolic acidosis compared to the control group (31.7% vs. 36.8%, respectively; p < .001). No whole blood CN levels above the lower limit of quantification were detected in any of the 51 patients with validated CN data. Plasma and urinary thiocyanate levels were also low.ConclusionsOur findings suggest that SNP, when used for short-term deliberate hypotension, does not cause an increased incidence of metabolic acidosis compared with the use of anesthetic agents alone.Trial registrationTrial registration numberNCT00135668.

Project description:The chronic overexpression of matrix metalloproteases leading to consequent degradation and loss of the elastic matrix with the reduction in tissue elasticity is central to the pathophysiology of proteolytic disorders, such as abdominal aortic aneurysms (AAAs), which are localized rupture-prone aortic expansions. Effecting tissue repair to alleviate this condition is contingent on restoring elastic matrix homeostasis in the aortic wall. This is naturally irreversible due to the poor elastogenicity of adult and diseased vascular cells, and the impaired ability to assemble mature elastic fibers, more so in the context of phenotypic changes to medial smooth muscle cells (SMCs) owing to the loss of nitric oxide (NO) signaling in the AAA wall tissue. In this study, we report the benefits of the exposure of primary human aneurysmal SMCs (aHASMCs) to NO donor drug, sodium nitroprusside (SNP), in improving extracellular matrix homeostasis, particularly aspects of elastic fiber assembly, and inhibition of proteolytic degradation. SNP treatment (100 nM) upregulated elastic matrix regeneration at both gene (p < 0.05) and protein levels (p < 0.01) without affecting cell proliferation, improved gene, and protein expression of crosslinking enzyme, lysyl oxidase (p < 0.05), inhibited the expression of MMP2 (matrix metalloprotease 2) significantly (p < 0.05) and promoted contractile SMC phenotypes in aHASMC culture. In addition, SNP also attenuated the expression of mitogen-activated protein kinases, a significant player in AAA formation and progression. Our results indicate the promise of SNP for therapeutic augmentation of elastic matrix regeneration, with prospects for wall repair in AAAs. Impact Statement Chronic and naturally irreversible enzymatic degradation and loss of elastic fibers are centric to proteolytic disorders such as abdominal aortic aneurysms (AAAs). This is linked to poor elastogenicity of adult and diseased vascular cells, compromising their ability to assemble mature elastic fibers. Toward addressing this, we demonstrate the phenotype-modulatory properties of a nitric oxide donor drug, sodium nitroprusside on aneurysmal smooth muscle cells, and its dose-specific proelastogenic and antiproteolytic properties for restoring elastic matrix homeostasis. Combined with the development of vehicles for site-localized, controlled drug delivery, this can potentially lead to a new nonsurgical approach for AAA wall repair in the future.

Project description:BackgroundDeliberate hypotension is used to provide a bloodless field during functional endoscopic sinus surgery; however, the impact of controlled hypotension during anesthesia on peripheral tissue perfusion has not been extensively evaluated. The aim of this study was to compare the impact of nitroglycerin- versus labetalol-induced hypotension on peripheral perfusion.MethodsThe present randomized, double-blinded, controlled trial included adult patients undergoing endoscopic sinus surgery. Patients were allocated to one of two groups according to the drug received for induction of deliberate hypotension: nitroglycerin (n = 20) or labetalol (n = 20). Mean arterial pressure was maintained at 55-65 mmHg in both groups. Both study groups were compared according to pulse oximeter-derived peripheral perfusion index (primary outcome), serum lactate level, mean arterial pressure, heart rate, surgical field score, and intraoperative blood loss.ResultsForty patients were included in the final analysis. The nitroglycerin group exhibited a higher peripheral perfusion index at nearly all records (p < 0.0001) and lower postoperative serum lactate levels (1.3 ± 0.2 mmol/L vs. 1.7 ± 0.4 mmol/L; p = 0.001) than the labetalol group. The peripheral perfusion index was higher in the nitroglycerin group than at baseline at most intraoperative readings. The median surgical field score was modestly lower in the labetalol group than in the nitroglycerin group in the first 20 min (2 [interquartile range (IQR) 2-2.5] versus 1.5 [IQR 1-2]; p = 0.001). Both groups demonstrated comparable and acceptable surgical field scores in all subsequent readings.ConclusionNitroglycerin-induced deliberate hypotension was accompanied by higher peripheral perfusion index and lower serum lactate levels than labetalol-induced deliberate hypotension during sinus endoscopic surgery.Trial registrationThe study was registered at clinicaltrials registry system with trial number: NCT03809065. Registered at 19 January 2019. This study adheres to CONSORT guidelines.

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Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

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Evaluation of sodium nitroprusside for controlled hypotension in children during surgery.

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