Vetnews | Februarie 2025 10 « BACK TO CONTENTS apneustic plateau control unit, created to mimic the breath-holding apneustic breathing pattern of cetaceans. Apneustic plateau ventilation, as coined by Ridgway and McCormick, enabled rapid lung inflation with an inspiratory breath hold at approximately 20– 24 mmHg pressure for 15–30 s, followed by airway pressure release, and rapid re-inflation (Ridgway et al., 1974; Ridgway & McCormick, 1971, 1967). Early ventilation practices using conventional modes of ventilation would result in decreasing trends towards hypoxemia due to hypoventilation (Ridgway et al., 1974). Thus, apneustic plateau ventilation was the standardized approach for mechanical ventilation of dolphins. Anesthetic practices in the 60s and 70s evaluated the use of a low solubility anesthetic gas, nitrous oxide, for maintaining a surgical plane of anesthesia. This minimally potent inhalational anesthetic was often combined with a neuromuscular blocking agent (succinylcholine) and a parenteral barbiturate (thiopental) in dolphins. However, a mixed gas anesthetic protocol of 60% nitrous oxide with 40% oxygen did not result in a surgical plane of anesthesia. In one study, an increase to 80% nitrous oxide resulted in lost reflexes and complete unconsciousness following an initial period of hyperexcitability (Ridgway & McCormick, 1971). In a separate study, persistent reflexes and visual tracking at the same concentration of nitrous gas mixture was reported (Ridgway & McCormick, 1967). Further, at 80% nitrous oxide, hypoxemia and cyanosis of the mucus membranes were observed. The combination of continued presence of consciousness and inadequate oxygenation at high inspired nitrous oxide concentrations, led Ridgway and colleagues to cite the nitrous gas mixture as inadequate for major surgery in dolphins, especially as a sole anesthetic agent (Ridgway & McCormick, 1967). Early hemodynamic studies in these anesthetized dolphins provided insights into cardiovascular function under general anesthesia. Mean arterial pressures in healthy dolphins on halothane gas anesthesia averaged 115 mmHg (normal reported as 120–140 mmHg) (Ridgway & McCormick, 1971). Dolphins on nitrous oxide-oxygen gas anesthesia ranged between 122 and 142 mmHg (Sommer et al., 1968). Ridgway also observed that the normal, respiratory sinus arrhythmia (RSA) observed in the conscious, nonanesthetized dolphin transitioned to a normal sinus rhythm, with heart rates between 80 and 160 bpm, after thiopental (15–25 mg/ kg) administration (Ridgway et al., 1974; Ridgway & McCormick, 1971, 1967). While Ridgway published on observational aspects of clinical anesthesia in dolphins, few comprehensive and controlled physiologic studies of anesthetized dolphins have since been conducted (McCormick, 1969; Sommer et al., 1968). Most reports are limited to single case descriptions that document individual dolphins (Tursiops spp.) recovering from surgical or diagnostic procedures, rather than controlled pharmacokinetic or physiologic studies on the effects of ventilation and anesthetics agents (Table 2) (Bailey, 2021; Doescher et al., 2018; Dover et al., 1999; Lee et al., 2019; Lindemann et al., 2023; Meegan et al., 2015, 2016; Meegan, Miller, et al., 2021; Ridgway, 2002; Russell et al., 2021; Schmitt et al., 2014; Tamura et al., 2017). The paucity of comprehensive, controlled anesthetic studies in bottlenose dolphins remain a hurdle in our understanding of the physiology of anesthesia in this species. 3. MECHANISMS AND CURRENT APPROACHES TO DOLPHIN ANESTHESIA Anesthetic and analgesic agents modulate the central nervous system (CNS) via activity on gamma-aminobutyric acid type A (GABAA), N-methyl D-aspartate (NMDA), adrenergic alpha-2, and opioid receptors. Ion channels, such as the family of neuronal hyperpolarization-activated cyclic nucleotide-gated (HCM) and two-pore domain potassium (K2P) channels, are also known targets for anesthetic agents (Cascella et al., 2020; Pavel et al., 2020). For example, the excitatory glutamate NMDA receptor is associated with neuropathic pain and is antagonized by dissociative anesthetics like ketamine, tiletamine, and phencyclidine. The GABAA receptors are targets for the CNS inhibitory effects of propofol, etomidate, alfaxalone, barbiturates, and benzodiazepines. Alpha-2 adrenergic agonists, such as dexmedetomidine, tizanidine, and clonidine, produce effects centrally within the locus coeruleus (sedation) and dorsal horn (pain), as well as peripherally to modulate blood pressure, cardiac output, and insulin release from the pancreatic beta cells (Giovannitti Jr et al., 2015). Opioids (morphine, codeine, methadone, tramadol, meperidine, butorphanol, buprenorphine) exert their effects at central and peripheral mu, kappa, and delta opioid receptors and can cause hypotension and sinus bradycardia through depression of sinoatrial node activity. However, the most notable and often critical effects of opioids are seen as centrally-mediated depression of the respiratory centers, whereby hypoventilation can lead to life-threatening hypercapnia. Volatile anesthetics, like sevoflurane, isoflurane, and desflurane, depress the response to carbon dioxide in a dose-dependent fashion and may cause sedation, in part, by inhibiting cholinergic neurotransmission in regions of the brain that regulate arousal (Vacas et al., 2013). With these mechanisms in mind, current approaches to anesthesia of bottlenose dolphins may present several physiologic challenges for the anesthetist. The use of drugs causing and contributing to cardiopulmonary depression, as is also seen in large terrestrial mammals, is an undesired consequence leading to a variety of anesthesia-associated co-morbidities (Bukoski et al., 2022; GozaloMarcilla et al., 2014; Menzies et al., 2016; Sage et al., 2018). Currently, no literature exists on the cardiopulmonary impacts of anesthesia protocols on dolphins. Per the experience of the authors, cardiopulmonary derangements, such as hypoventilation, ventilation-perfusion mismatch, decreased functional residual capacity (FRC), vasodilation, and depression of cardiac contractility are often observed in anesthetized dolphins using commonly accepted anesthetic drugs (e.g., opioids, propofol, benzodiazepines, and inhalation anesthetics) and protocols (e.g., various combinations of ventilation methods and drug selection). These effects can often lead to hypoxemia, hypercapnia, hypotension, and decreased cardiac output (Berry, 2015; Haskins, 2015; Steffey et al., 2015). If not properly mitigated, these effects can impair organ perfusion, reduce oxygen delivery, and predispose the dolphin to organ injury and myopathic conditions (Bailey, 2021; Dold & Ridgway, 2014; Haulena & Schmitt, 2018). For example, decreased work of breathing and subsequent respiratory depression is a characteristic of dolphin sedation (benzodiazepines and opioids) that often demands respiratory support in the form of mechanical ventilation (Dold & Ridgway, 2014; Ridgway & McCormick, 1971, 1967). The use Leading Article
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