Maternal and Preterm Fetal Sheep Responses to Dexmedetomidine

Abstract

Topics: Pharmacology P regnant women may require sedation, anesthesia, or pain control for nonobstetric-related care. The a 2adrenergic receptor (a 2 AR) agonist dexmedetomidine (DEX) has sedative, anxiolytic, and analgesic actions and can reduce the dose requirements for other sedative and analgesic drugs through synergistic effects with opioids and benzodiazepines. Clinical investigations of DEX have not included significant numbers of pregnant patients; in fact, most studies have excluded pregnant women. This study was designed to determine the maternal and fetal responses to an intravenous infusion of DEX in sheep.The study was performed on 9 preterm pregnant ewes at gestational day 92, a time relatively equivalent to the end of the second trimester in humans. Surgical anesthesia was induced with IV sodium thiopental and maintained with isoflurane in oxygen. Standard surgical techniques were used to insert catheters into maternal femoral artery and jugular vein as well as bilateral fetal femoral arteries. A flow probe was placed around the left uterine artery to record uterine blood flow (UBF). The fetal head was exteriorized to install near-infrared spectroscopy probes to assess changes in fetal cerebral oxygenation during and after drug administration to the mother. The fetus was then returned to the uterus. After the procedure, infiltration of the surgical incision with bupivacaine and intramuscular nalbuphine hydrochloride were used to control postoperative pain. Animals recovered for 48 hours before the DEX-exposure experiment was conducted. Maternal and fetal cardiovascular data along with UBF were recorded. Fetal cerebral oxygenation, measured by changes in oxygenated, deoxygenated, and total hemoglobin (Hb) (oxyHb, deoxyHb, and totalHb, respectively), was quantitated with the near-infrared spectroscopy monitor. After a baseline recording period of 30 to 60 minutes, drug exposure was begun using human-dosing guidelines. Each ewe received an IV bolus injection of DEX, 1.0 mg/kg followed by a constant IV infusion of 1.0 mg/kg/h. The infusion was stopped after 3 hours and the experiment halted 2 hours later. Hemodynamic and fetal cerebral oxygenation data were continuously recorded during the study; maternal and fetal arterial blood samples were obtained at 30-minute intervals.The statistical analyses focused on the 3 primary endpoints: changes in fetal cerebral oxygenation, maternal and fetal cardiovascular status, and arterial blood gas status.All animals tolerated the DEX infusion with no complications during or after drug exposure. Profound sedation occurred within minutes of starting the infusion; consciousness returned within 30 to 60 minutes after discontinuation of the infusion. During the infusion, the sheep were unresponsive to painful stimuli. The ewes had a normal respiratory pattern throughout the exposure period, as evidenced by the arterial blood gas values that remained normal throughout the study. Only blood glucose levels in both the ewe and fetus continued to rise during DEX infusion, p...

Sedative and cardiorespiratory effects of detomidine constant rate infusion in sheep

“…1–5 Although this class of drugs is widely used, dose-dependent cardiopulmonary effects, such as decreased cardiac output (CO), bradyarrhythmia, peripheral vasoconstriction, biphasic arterial blood pressure response, respiratory depression, hypoxaemia and acute pulmonary oedema, have been observed. 6–11 Also, individual, breed or strain variability can influence the presence or absence of such effects. 7…”

“…8 In pregnant ewes and preterm foetal sheep, the infusion of dexmedetomidine produced satisfactory results for sedation and pain control, with minimal foetal response. 10 These studies did not evaluate the occurrence of hypoxaemia or other respiratory effects. However, the effects of detomidine CRI are yet to be reported.…”

Maternal and fetal arterial blood gas data during general anaesthesia for caesarean delivery of preterm twin lambs

“…Pregnant sheep and their fetuses are commonly utilized as animal models for investigations into human pregnancy and the causes and consequences of preterm birth. 1–4 As elegantly argued in Russell and Burch’s landmark work, The principles of humane experimental technique , the continual refinement of practice in animal-based research is key to minimizing the impact of research on animal welfare and to ensuring the integrity of scientific data. 5…”

Management of Labor Analgesia in a Patient with Acute Myeloid Leukemia

“…Second, it may worsen disease outcome; in studies of children with acute lymphoblastic leukemia undergoing diagnostic lumbar punctures and concurrent administration of intrathecal chemotherapy, those with a traumatic lumbar puncture, defined in one study as a sample containing >10 red blood cells per microliter, had worse event-free survival than their counterparts without CNS disease. 18 Dexmedetomidine may also offer several benefits to obstetric patients. [11][12][13][14] Thus, while the risk of spinal anesthesia in the patient with untreated AML is unknown, these studies would suggest that resultant worsening of oncologic outcome is possible.…”