Szmuk Peter, Andropoulos Dean, McGowan Francis, Brambrink Ansgar, Lee Christopher, Lee Katherine J, McCann Mary Ellen, Liu Yang, Saynhalath Rita, Bong Choon Looi, Anderson Brian J, Berde Charles, De Graaff Jurgen C, Disma Nicola, Kurth Dean, Loepke Andreas, Orser Beverley, Sessler Daniel I, Skowno Justin J, von Ungern-Sternberg Britta S, Vutskits Laszlo, Davidson Andrew
Department of Anesthesiology and Pain Management, University of Texas Southwestern and Children's Medical Centre Dallas, Dallas, Texas.
Department of Outcomes Research, Cleveland Clinic, Cleveland, Ohio.
Paediatr Anaesth. 2019 Jan;29(1):59-67. doi: 10.1111/pan.13544.
Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown. The aim of this study was to determine the feasibility of a remifentanil/dexmedetomidine/neuraxial block technique in infants scheduled for surgery lasting longer than 2 hours.
Sixty infants (age 1-12 months) were enrolled at seven centers over 18 months. A caudal local anesthetic block was placed after induction of anesthesia with sevoflurane. Next, an infusion of dexmedetomidine and remifentanil commenced, and the sevoflurane was discontinued. Three different protocols with escalating doses of dexmedetomidine and remifentanil were used.
One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another. The caudal block was unsuccessful in two infants. Of the 56 infants who completed the protocol, 45 (80%) had at least one episode of hypertension (mean arterial pressure >80 mm Hg) and/or movement that required adjusting the anesthesia regimen. In the majority of these cases, the remifentanil and/or dexmedetomidine doses were increased although six infants required rescue 0.3% sevoflurane and one required a propofol bolus. Ten infants had at least one episode of mild hypotension (mean arterial pressure 40-50 mm Hg) and four had at least one episode of moderate hypotension (mean arterial pressure <40 mm Hg).
A dexmedetomidine/remifentanil neuraxial anesthetic regimen was effective in 87.5% of infants. These findings can be used as a foundation for designing larger trials that assess alternative anesthetic regimens for anesthetic neurotoxicity in infants.
对麻醉药潜在神经毒性的担忧促使人们对使用潜在毒性较小的麻醉方案的前瞻性临床试验越来越感兴趣，尤其是对于婴儿的长时间麻醉。临床前研究表明，与其他传统麻醉方案相比，右美托咪定的神经毒性可能较低；然而，需要与麻醉药物（如瑞芬太尼）联合使用和/或进行区域阻滞才能为手术提供足够的麻醉。这种药理学方法的可行性尚不清楚。本研究的目的是确定瑞芬太尼/右美托咪定/神经轴阻滞技术在计划进行超过2小时手术的婴儿中的可行性。
在18个月内，七个中心招募了60名婴儿（年龄1至12个月）。在用七氟醚诱导麻醉后进行骶管局部麻醉阻滞。接下来，开始输注右美托咪定和瑞芬太尼，并停用七氟醚。使用了三种不同的方案，右美托咪定和瑞芬太尼的剂量逐渐增加。
一名婴儿因违反方案被排除，另一名在麻醉前撤回了同意书。两名婴儿的骶管阻滞未成功。在完成方案的56名婴儿中，45名（80%）至少有一次高血压发作（平均动脉压>80 mmHg）和/或需要调整麻醉方案的动作。在大多数这些病例中，增加了瑞芬太尼和/或右美托咪定的剂量，尽管有六名婴儿需要抢救性使用0.3%的七氟醚，一名婴儿需要推注丙泊酚。十名婴儿至少有一次轻度低血压发作（平均动脉压40至50 mmHg），四名婴儿至少有一次中度低血压发作（平均动脉压<40 mmHg）。
右美托咪定/瑞芬太尼神经轴麻醉方案在87.5%的婴儿中有效。这些发现可作为设计更大规模试验的基础，以评估婴儿麻醉神经毒性的替代麻醉方案。
