An open label pilot study of a dexmedetomidine‐remifentanil‐caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study

Abstract

Summary Background 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. Methods 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. Results One infant was excluded due to a protocol violation and consent was withdrawn prior to anesthesia in another.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). Conclusion 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.

Use of dexmedetomidine and opioids as the primary anesthetic in infants and young children: A retrospective cohort study

“…In addition to demonstrating satisfactory anesthesia with dexmedetomidine and opioids with or without low‐dose (<1 minimum alveolar concentration) sevoflurane, our findings demonstrate that the frequency of intraoperative complications with these medications is low. The incidence of at least one episode of hypotension was 7% in the cohort, similar to the TREX pilot 2 (which utilized a dexmedetomidine‐remifentanil‐regional anesthetic combination), and the incidence of at least one episode of light anesthesia was 63%, which was lower than the TREX pilot. In contrast, we found a higher incidence of bradycardia (28%), but only 3.7% in the cohort required treatment.…”

“…Moreover, a few case reports in neonates and young children have described the feasibility of anesthesia with dexmedetomidine‐remifentanil in different clinical scenarios 12‐14 . Recently, a dexmedetomidine‐remifentanil and neuraxial anesthetic regimen (TREX pilot) was found effective in 87% of infants (aged 1‐12 months) undergoing lower abdominal or lower extremity surgery 2 . Another large randomized multicenter trial (TREX) is currently underway to examine the impact on IQ at age 3 of a standard sevoflurane‐based general anesthetic vs a low‐dose sevoflurane anesthetic combined with remifentanil and dexmedetomidine infusions in children under the age of 2 undergoing surgery lasting at least 2 hours (Clinicaltrials.gov NCT03089905).…”

“…Recently, a pilot‐study published by the TREX consortium investigated the feasibility of an alternative anesthetic in children, based on dexmedetomidine, remifentanil, and a regional anesthesia block. The study found that in 60 children, between 1 and 12 months of age, this combination is a clinically feasible anesthetic technique 2 . Additionally, a recent survey showed that 75% of the pediatric anesthesiologists in Europe, Australia, and the United States use dexmedetomidine in clinical practice, with more than half administering it without proper training or a protocol 3…”

General anesthesia affecting on developing brain: evidence from animal to clinical research

“…Different drugs are being studied to mitigate the apoptosis response to ASAs. Xenon and Dexmedetomidine (DEX) are already used in clinical settings as neuroprotection and anaesthetic sparing-effect, but more research is still needed [48][49][50][51].…”

General Anesthesia Affecting on Developing Brain: Evidence from Animal to Clinical Research

“…Different drugs are being studied to mitigate the apoptosis response to ASAs. Xenon and Dexmedetomidine (DEX) are already used in clinical settings as neuroprotection and anaesthetic sparing-effect, but more research is still needed [47][48][49][50][51].…”