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The Canadian Veterinary Journal = La... Feb 2020This case highlights the successful recovery to discharge of a hypothermic cat in cardiac arrest, with minimal lasting clinical signs. Immediately after resuscitation,...
This case highlights the successful recovery to discharge of a hypothermic cat in cardiac arrest, with minimal lasting clinical signs. Immediately after resuscitation, the cat was blind and non-ambulatory paraparetic. Within 4 days, the cat became fully ambulatory, but vision loss remains. We believe that the cat's hypothermia likely contributed to this successful outcome. Other factors which may have played a role in the cat's recovery were the administration of mannitol and anti-seizure medications. Key clinical message: We share learning points regarding re-warming rates for hypothermic patients and the use of Doxapram for stimulation of the central respiratory center.
Topics: Animals; Cardiopulmonary Resuscitation; Cat Diseases; Cats; Heart Arrest; Hypoglycemic Agents; Hypothermia
PubMed: 32020934
DOI: No ID Found -
Anesthesiology Sep 2014Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Opioid-induced respiratory depression is potentially lethal. GAL021 is a calcium-activated potassium (BKCa) channel blocker that causes reversal of opioid-induced respiratory depression in animals due to a stimulatory effect on ventilation at the carotid bodies. To assess in humans whether GAL021 stimulates breathing in established opioid-induced respiratory depression and to evaluate its safety, a proof-of-concept double-blind randomized controlled crossover study on isohypercapnic ventilation (study 1) and subsequent double-blind exploratory study on poikilocapnic ventilation and nonrespiratory end points (study 2) was performed.
METHODS
In study 1, intravenous low- and high-dose GAL021 and placebo were administrated on top of low- and high-dose alfentanil-induced respiratory depression in 12 healthy male volunteers on two separate occasions. In study 2, the effect of GAL021/placebo on poikilocapnic ventilation, analgesia, and sedation were explored in eight male volunteers. Data are mean difference between GAL021 and placebo (95% CI).
RESULTS
Study 1: Under isohypercapnic conditions, a separation between GAL021 and placebo on minute ventilation was observed by 6.1 (3.6 to 8.6) l/min (P < 0.01) and 3.6 (1.5 to 5.7) l/min (P < 0.01) at low-dose alfentanil plus high-dose GAL021 and high-dose-alfentanil plus high-dose GAL021, respectively. Study 2: Similar observations were made on poikilocapnic ventilation and arterial pCO2. GAL021 had no effect on alfentanil-induced sedation, antinociception and no safety issues or hemodynamic effects became apparent.
CONCLUSION
GAL021 produces respiratory stimulatory effects during opioid-induced respiratory depression with containment of opioid-analgesia and without any further increase of sedation. Further studies are needed to confirm these preliminary data.
Topics: Adolescent; Adult; Alfentanil; Analgesia; Analgesics, Opioid; Cross-Over Studies; Double-Blind Method; Doxapram; Healthy Volunteers; Hemodynamics; Humans; Large-Conductance Calcium-Activated Potassium Channels; Male; Middle Aged; Potassium Channel Blockers; Respiratory Insufficiency; Triazines
PubMed: 25222672
DOI: 10.1097/ALN.0000000000000367 -
Veterinary Anaesthesia and Analgesia Sep 2016To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride. (Comparative Study)
Comparative Study
OBJECTIVES
To determine whether CX1942 reverses respiratory depression in etorphine-immobilized goats, and to compare its effects with those of doxapram hydrochloride.
STUDY DESIGN
A prospective, crossover experimental trial conducted at 1753 m.a.s.l.
ANIMALS
Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg.
METHODS
Following immobilization with 0.1 mg kg(-1) etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO2 , PaCO2 , pH and SaO2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes.
RESULTS
Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute(-1) above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO2 and SaO2 in comparison with the control trial.
CONCLUSIONS
CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats.
CLINICAL RELEVANCE
Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.
Topics: Analgesics, Opioid; Animals; Doxapram; Etorphine; Female; Goats; Hypoxia; Immobilization; Naltrexone; Narcotic Antagonists; Receptors, AMPA; Respiratory Insufficiency; Respiratory System Agents
PubMed: 27531058
DOI: 10.1111/vaa.12358 -
Sleep Jan 2021Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus...
Modulation of TASK-1/3 channels at the hypoglossal motoneuron pool and effects on tongue motor output and responses to excitatory inputs in vivo: implications for strategies for obstructive sleep apnea pharmacotherapy.
Obstructive sleep apnea (OSA) occurs exclusively during sleep due to reduced tongue motor activity. Withdrawal of excitatory inputs to the hypoglossal motor nucleus (HMN) from wake to sleep contributes to this reduced activity. Several awake-active neurotransmitters with inputs to the HMN (e.g. serotonin [5-HT]) inhibit K+ leak mediated by TASK-1/3 channels on hypoglossal motoneurons, leading to increased neuronal activity in vitro. We hypothesize that TASK channel inhibition at the HMN will increase tongue muscle activity in vivo and modulate responses to 5-HT. We first microperfused the HMN of anesthetized rats with TASK channel inhibitors: doxapram (75 μM, n = 9), A1899 (25 μM, n = 9), ML365 (25 μM, n = 9), acidified artificial cerebrospinal fluid (ACSF, pH = 6.25, n = 9); and a TASK channel activator terbinafine (50 μM, n = 9); all with and without co-applied 5-HT (10 mM). 5-HT alone at the HMN increased tongue motor activity (202.8% ± 45.9%, p < 0.001). However, neither the TASK channel inhibitors, nor activator, at the HMN changed baseline tongue activity (p > 0.716) or responses to 5-HT (p > 0.127). Tonic tongue motor responses to 5-HT at the HMN were also not different (p > 0.05) between ChAT-Cre:TASKf/f mice (n = 8) lacking TASK-1/3 channels on cholinergic neurons versus controls (n = 10). In freely behaving rats (n = 9), microperfusion of A1899 into the HMN increased within-breath phasic tongue motor activity in wakefulness only (p = 0.005) but not sleep, with no effects on tonic activity across all sleep-wake states. Together, the findings suggest robust maintenance of tongue motor activity despite various strategies for TASK channel manipulation targeting the HMN in vivo, and thus currently do not support this target and direction for potential OSA pharmacotherapy.
Topics: Animals; Hypoglossal Nerve; Mice; Motor Neurons; Rats; Rats, Wistar; Sleep Apnea, Obstructive; Tongue
PubMed: 32745213
DOI: 10.1093/sleep/zsaa144 -
Psychiatry Research May 2016
Topics: Arousal; Central Nervous System Stimulants; Doxapram; Heart Rate; Humans; Panic Disorder
PubMed: 26952828
DOI: 10.1016/j.psychres.2016.03.002 -
The Journal of Experimental Biology Apr 2016To determine the costs of pulmonary ventilation without imposing severe oxygen limitations or acidosis that normally accompany exposures to hypoxia or hypercapnia, we...
To determine the costs of pulmonary ventilation without imposing severe oxygen limitations or acidosis that normally accompany exposures to hypoxia or hypercapnia, we opted to pharmacologically stimulate ventilation with doxapram (5 and 10 mg kg(-1)) in alligators. Doxapram is used clinically to alleviate ventilatory depression in response to anaesthesia and acts primarily on the peripheral oxygen-sensitive chemoreceptors. Using this approach, we investigated the hypothesis that pulmonary ventilation is relatively modest in comparison to resting metabolic rate in crocodilians and equipped seven juvenile alligators with masks for concurrent determination of ventilation and oxygen uptake. Doxapram elicited a dose-dependent and up to fourfold rise in ventilation, primarily by increasing ventilatory frequency. The accompanying rise in oxygen uptake was very small; ventilation in resting animals constitutes no more than 5% of resting metabolic rate. The conclusion that pulmonary ventilation is energetically cheap is consistent with earlier studies on alligators where ventilation was stimulated by hypoxia or hypercapnia.
Topics: Alligators and Crocodiles; Animals; Basal Metabolism; Doxapram; Oxygen Consumption; Pulmonary Ventilation; Respiratory Rate; Respiratory System Agents; United States
PubMed: 26896538
DOI: 10.1242/jeb.135871 -
Veterinary Anaesthesia and Analgesia Nov 2015To compare the agreement, repeatability and trending ability of transpulmonary thermodilution (TPTD) and pulmonary artery thermodilution (PATD) cardiac output (Q˙t)... (Comparative Study)
Comparative Study Randomized Controlled Trial
OBJECTIVE
To compare the agreement, repeatability and trending ability of transpulmonary thermodilution (TPTD) and pulmonary artery thermodilution (PATD) cardiac output (Q˙t) measurements in unsedated newborn calves.
STUDY DESIGN
Prospective experimental trial.
ANIMALS
Eight newborn calves weighing a median (range) of 53 (46-59) kg.
METHODS
Pulmonary and femoral artery thermodilution catheters were placed under local anaesthesia. A total of 382 PATD and TPTD Q˙t measurements were performed simultaneously. Cardiac output was influenced by intravenous doxapram and theophylline in a randomized crossover fashion. Bland-Altman analysis for multiple comparisons, concordance and polar plots were used to assess TPTD against PATD.
RESULTS
Median (range) cardiac index values measured with PATD and TPTD were 197 mL kg(-1) minute(-1) (74-335 mL kg(-1) minute(-1)) and 196 mL kg(-1) minute(-1) (59-395 mL kg(-1) minute(-1)), respec-tively. A small mean bias of -3 mL kg(-1) minute(-1) with limits of agreement (LOA) of -64 to 58 mL kg(-1) minute(-1) and a percentage error of 31% were found. Eighty-two mean values were calculated. This reduced the LOA to -50 to 41 mL kg(-1) minute(-1) with a similar small bias and a percentage error of 23%. Mean TPTD tracked changes in Q˙t compared with mean PATD with 90% concordance, a mean polar angle of 6° and radial LOA of 43°, indicating marginal trending ability. Keeping the femoral artery catheter patent and obtaining acceptable measurements were very challenging because the calves were not used to being restrained. Calf movement had less influence on PATD.
CONCLUSIONS AND CLINICAL RELEVANCE
We recommend that PATD remains the reference method to measure Q˙t in unsedated newborn calves. However, the robust results of the evaluation of the less invasive TPTD technique warrants further evaluation taking into account the difficulties reported in this study.
Topics: Animals; Animals, Newborn; Cardiac Output; Cattle; Central Nervous System Stimulants; Cross-Over Studies; Doxapram; Female; Femoral Artery; Male; Pulmonary Artery; Theophylline; Thermodilution; Vasodilator Agents
PubMed: 25689575
DOI: 10.1111/vaa.12243 -
The American Journal of Emergency... Mar 2017
Topics: Adjuvants, Anesthesia; Administration, Intravenous; Aged; Central Nervous System Stimulants; Coma; Doxapram; Humans; Male; Sodium Oxybate
PubMed: 27641247
DOI: 10.1016/j.ajem.2016.09.010 -
Archives of Disease in Childhood. Fetal... Jan 2020During delayed umbilical cord clamping, the factors underpinning placental transfusion remain unknown. We hypothesised that reductions in thoracic pressure during...
INTRODUCTION
During delayed umbilical cord clamping, the factors underpinning placental transfusion remain unknown. We hypothesised that reductions in thoracic pressure during inspiration would enhance placental transfusion in spontaneously breathing preterm lambs.
OBJECTIVE
Investigate the effect of spontaneous breathing on umbilical venous flow and body weight in preterm lambs.
METHODS
Pregnant sheep were instrumented at 132-133 days gestational age to measure fetal common umbilical venous, pulmonary and cerebral blood flows as well as arterial and intrapleural (IP) pressures. At delivery, doxapram and caffeine were administered to promote breathing. Lamb body weights were measured continuously and breathing was assessed by IP pressure changes.
RESULTS
In 6 lambs, 491 out of 1117 breaths were analysed for change in body weight. Weight increased in 46.6% and decreased in 47.5% of breaths. An overall mean increase of 0.02±2.5 g per breath was calculated, and no net placental transfusion was observed prior to cord clamping (median difference in body weight 52.3 [-54.9-166.1] g, p=0.418). Umbilical venous (UV) flow transiently decreased with each inspiration, and in some cases ceased, before UV flow normalised during expiration. The reduction in UV flow was positively correlated with the standardised reduction in (IP) pressure, increasing by 109 mL/min for every SD reduction in IP pressure. Thus, the reduction in UV flow was closely related to inspiratory depth.
CONCLUSIONS
Spontaneous breathing had no net effect on body weight in preterm lambs at birth. UV blood flow decreased as inspiratory effort increased, possibly due to constriction of the inferior vena cava caused by diaphragmatic contraction, as previously observed in human fetuses.
Topics: Animals; Animals, Newborn; Blood Flow Velocity; Body Weight; Constriction; Disease Models, Animal; Female; Placental Circulation; Pregnancy; Premature Birth; Respiration; Sheep; Time Factors; Umbilical Cord; Umbilical Veins
PubMed: 31092674
DOI: 10.1136/archdischild-2018-316044 -
Journal of Zoo and Wildlife Medicine :... Mar 2017This report describes the anesthetic management of a 14-yr-old, 160-kg, female Indo-Pacific bottlenose dolphin ( Tursiops aduncus ) that underwent surgical debridement...
This report describes the anesthetic management of a 14-yr-old, 160-kg, female Indo-Pacific bottlenose dolphin ( Tursiops aduncus ) that underwent surgical debridement for a refractory subcutaneous abscess twice within a 6-mo interval. The animal was otherwise in good physical condition at each anesthetic procedure. Following premedication with intramuscular midazolam and butorphanol, anesthesia was induced with propofol and maintained with sevoflurane by intubation. During surgery ventilation was controlled. Blood pressure was indirectly estimated using either oscillometric or pulse oximetry. Presumed hypotension was managed by adjusting the sevoflurane concentration and infusion of dopamine. During recovery, the dolphin regained adequate spontaneous respiration following intravenous administration of flumazenil and doxapram. The dolphin was extubated at 85 min and 53 min after the first and second surgeries, respectively. Successful weaning from the ventilator and initiation of spontaneous respiration was the most important complication encountered. Establishment of a reliable blood pressure measurement technique is critical to success for anesthesia in this species.
Topics: Abscess; Adjuvants, Anesthesia; Analgesics, Opioid; Anesthesia; Anesthetics, Inhalation; Animals; Bottle-Nosed Dolphin; Butorphanol; Debridement; Female; Hypnotics and Sedatives; Methyl Ethers; Midazolam; Propofol; Sevoflurane; Staphylococcal Infections; Staphylococcus aureus; Tail
PubMed: 28363054
DOI: 10.1638/2016-0088.1