The immune response to anesthesia: Part 1

ObjectiveTo review the immune response to anesthesia including mechanical ventilation, inhaled anesthetic gases, and injectable anesthetics and sedatives.Study designReview.Methods and databasesMultiple literature searches were performed using PubMed and Google Scholar from spring 2012 through fall 2013. Relevant anesthetic and immune terms were used to search databases without year published or species constraints. The online database for Veterinary Anaesthesia and Analgesia and the Journal of Veterinary Emergency and Critical Care were searched by issue starting in 2000 for relevant articles.ConclusionRecent research data indicate that commonly used volatile anesthetic agents, such as isoflurane and sevoflurane, may have a protective effect on vital organs. With the lung as the target organ, protection using an appropriate anesthetic protocol may be possible during direct pulmonary insults, including mechanical ventilation, and during systemic disease processes, such as endotoxemia, generalized sepsis, and ischemia-reperfusion injury.     

A systematic review of the effects of injectable sedative and anesthetic drugs and inhalant anesthetics on intraocular pressure in the dog

ObjectiveThe purpose of this systematic review was to summarize the results of studies that have determined the effect of injectable and inhalant drugs used in anesthesia on intraocular pressure (IOP) in dogs.Databases usedA comprehensive search of research literature was performed without language restriction. The search utilized the PubMed, CAB Abstracts and the University of Georgia’s Galileo electronic databases using a combination of free text terms ‘Ophthalmology’, ‘Intraocular Pressure’, ‘Anesthetic’, ‘Anesthesia’, ‘Canine’ or ‘Dog’. The time frame searched was from 1970 to October 2018. Any published research paper that dealt with sedatives or anesthetics administered systemically and the canine eye was evaluated.ConclusionsThe effects of many anesthetic drugs in dogs with ocular pathology are largely unknown. Many anesthetic drugs do not induce clinically relevant changes in IOP in dogs with normal eyes, although some studies demonstrated results with statistically significant changes. The dose, route of administration, experimental conditions, drug combinations, timing of measurements, measurement technology and setting or individual animal characteristics may all produce some heterogeneity in results from multiple studies.     

Anesthetic and analgesic techniques used for cats undergoing ovariohysterectomies in general practice in the United States

ObjectiveTo better document anesthetic and analgesic protocols used by veterinarians in general practice within the United States (US) when performing elective ovariohysterectomy in cats.Study designCross-sectional survey.PopulationVeterinary practitioners in the US who are members of the Veterinary Information Network Inc. (VIN).MethodsAn online anonymous survey was distributed to VIN members. The survey included questions pertaining to preanesthetic evaluation, premedication, induction, monitoring and maintenance protocols, and postoperative analgesia and sedation protocols when performing ovariohysterectomy in cats.ResultsA total of 1324 veterinarians completed the survey. Respondents (number; %) reported performing preanesthetic laboratory tests [packed cell volume (256; 19.3%), complete blood cell count (893; 67.4%) and biochemistry panels (1101; 83.2%)] and preanesthetic examinations (1186; 89.6%) on the morning of surgery. The most frequently administered drugs for premedication were dexmedetomidine (353; 26.7%) and buprenorphine (424; 32.0%). The most frequently administered induction agent was propofol (451; 61.3%), and isoflurane (668; 50.4%) was the most common agent for maintenance of anesthesia. The majority of respondents reported placing intravenous catheters (885; 66.8%), administering crystalloid fluids (689; 52.0%) and providing heat support (1142; 86.3%). Participants reported using perioperative and postoperative analgesia including opioids (791; 59.7%), non-steroidal anti-inflammatory drugs (NSAIDs; 697; 52.6%) and NSAIDs dispensed for home use (665; 50.2%). Cats were commonly released home on the day of surgery (1150; 86.9%), and most participants reported contacting owners for follow-up within 1–2 days (989; 74.7%).Conclusions and clinical relevanceAnesthetic protocols and management techniques for routine feline ovariohysterectomy differ widely among US veterinarians who are VIN members, and results from this study may be of use to evaluate anesthetic practices from this population of veterinarians.     

Comparison of several combinations for anesthesia in rabbits.

Few safe and effective anesthesia regimens have been described for use in rabbits, partially because of the susceptibility of this species to sometimes fatal respiratory depression. Although inhalant anesthetics are generally safer than injectable anesthetics, their use may be limited by lack of equipment or facilities. This study was conducted to compare effects of several injectable anesthetics in rabbits on response to noxious stimuli, heart rate, respiratory rate, and rectal temperature. Six injectable anesthetic combinations were administered to rabbits: xylazine-ethyl-(1-methyl-propyl) malonyl-thio-urea salt (EMTU), ketamine-EMTU, xylazine-pentobarbital, xylazine-acepromazine-ketamine (XAK), ketamine-chloral hydrate, and ketamine-xylazine. All combinations induced a depression of respiratory rate. Although rectal temperature values were reduced to some degree in each group, the most profound hypothermia was induced by XAK. The combination that induced the longest duration of anesthesia was XAK. It was concluded that XAK was preferable for longer periods of anesthesia (60 to 120 minutes), although it induces severe hypothermia. For short periods of anesthesia, xylazine-pentobarbital, xylazine-EMTU, or ketamine-xylazine were deemed adequate; however, xylazine-EMTU induced the best survivability and consistency.     

Sedation and anesthesia of pet rabbits

Pet rabbits frequently become stressed when handled and may require sedation or chemical immobilization for procedures such as blood collection, IV catheter placement, radiography, deep ear cleaning, and dentistry. Common surgical procedures requiring general anesthesia include spay, castration, gastrotomy, cystotomy, and orthopedic procedures. Rabbits may be difficult to safely sedate or anesthetize. Individual rabbits may have varying sensitivity to the depressant effects of anesthetics. The apparent sensitivity of the rabbit's respiratory center to anesthetic drugs and the narrow range between anesthetic and toxic doses in this species add to the unpredictable character of rabbit anesthesia. Furthermore, mortality following anesthesia and surgery in sick rabbits is common. Strategically, safe anesthesia of rabbits must include the planning of procedures so that anesthetic time is minimized. Clinicians must be on guard for individual variation in response to drugs. Minimizing the use of cardiovascular depressant agents, use of agents with a high therapeutic index, and careful titration of doses to effect, along with thorough cardiorespiratory monitoring, will permit attainment of appropriate anesthetic depth with the widest margin of safety. This article presents several injectable and inhalant anesthetic protocols that may assist in effective management of many types of rabbit patient.     

Anesthetic and analgesic techniques used for dogs undergoing ovariohysterectomies in general practice in the United States

ObjectiveTo acquire information about anesthesia and analgesia protocols used by United States (US) veterinarians in primary care practices when performing routine ovariohysterectomy in dogs.Study designCross-sectional survey.PopulationPrimary care veterinarians in the US.MethodsAn online anonymous survey, originally created in New Zealand, was modified with permission and made available to Veterinary Information Network (VIN) members. The survey asked questions about performing ovariohysterectomy in healthy adolescent dogs in the categories of preanesthetic evaluation, premedication and induction protocols, maintenance protocols and monitoring equipment, and postoperative analgesic and sedation protocols and pain assessments.ResultsA total of 1213 US veterinarians completed the survey. Respondents (n; %) reported performing preoperative laboratory tests [packed cell volume (135; 11%), complete blood cell count (889; 73%) and biochemistry panels (1057; 87%)] and preanesthetic examinations on the morning of surgery (1083; 90%). The most commonly administered drugs for premedication were acepromazine (512; 42%), hydromorphone (475; 39%) or butorphanol (463; 38%), with propofol (637; 67%) for induction of anesthesia and isoflurane (882; 73%) for maintenance of anesthesia. Most veterinarians reported placing intravenous catheters (945; 78%), administering electrolyte solutions (747; 67%) and providing heat support (1160; 96%). Perioperative and postoperative analgesia included local anesthetics (545; 45%), opioids (844; 70%) and non-steroidal anti-inflammatory drugs (NSAIDs) (953; 79%); NSAIDs were dispensed for home use (985; 81%). Dogs were most frequently discharged on the day of surgery (1068; 88%) and the owners were contacted (914; 75%) for follow-up within 1–2 days.Conclusions and clinical relevanceAnesthetic management for routine ovariohysterectomy in dogs varies among US veterinary VIN members. Information from this study is useful for all veterinarians for comparison with their practice management and for teachers of veterinary anesthesia to continue to emphasize options for analgesia.     

The case for maintenance of general anesthesia with an inhalational agent.

Control of anesthetic depth is the primary advantage of general anesthesia with inhalational anesthetics as opposed to injectable agents. In addition, inhalational anesthetics provide good intraoperative stress reduction, adequate muscle relaxation, and an elimination pathway (lungs) independent of liver and kidney function. There is little postoperative respiratory depression and no rebound effect, which is sometimes seen with injectable anesthetics. The incidence of anesthetic-related toxicity is rare and is not considered a problem.     

Evaluation of parenteral drugs for anesthesia in the blue crab (Callinectes sapidus)

The objective of this study was to evaluate the efficacy and safety of several parenteral anesthetics in blue crabs (Callinectes sapidus). Thirty-one animals were administered one or more of the following drugs by injection into the hemolymph (i.v.) through an arthrodial membrane: etomidate, ketamine, lidocaine, pentobarbital, propofol, tiletamine-zolazepam, xylazine, and ketamine-xylazine. A subset of crabs received intracardiac ketamine. Etomidate had no effect. Lidocaine effects were ultrashort (<3 min). Pentobarbital had prolonged inductions (2 min) and often caused violent excitement and poor anesthesia. Propofol induced light anesthesia accompanied by distress and limb autotomy. Inductions with ketamine, xylazine, tiletamine-zolazepam, and ketamine-xylazine were usually fast (<60 sec). Their anesthetic effects were generally very short (5-10 min) but predictable, smooth, and with good muscle relaxation. The latter two protocols induced a deep plane of anesthesia more consistently but also more significant bradycardia. Intracardiac ketamine injection was fatal in four of five crabs. In conclusion, the anesthetic protocols were considered unsuitable for prolonged anesthesia. However, if very short-term anesthesia is desired, then tiletamine-zolazepam or ketamine-xylazine is recommended. Further studies are indicated to identify a safe anesthetic protocol of longer duration in C. sapidus as well as in other crab species.     

Cardiopulmonary effects of dexmedetomidine and ketamine infusions with either propofol infusion or isoflurane for anesthesia in horses

ObjectiveTo examine the cardiopulmonary effects of two anesthetic protocols for dorsally recumbent horses undergoing carpal arthroscopy.Study designProspective, randomized, crossover study.AnimalsSix horses weighing 488.3 ± 29.1 kg.MethodsHorses were sedated with intravenous (IV) xylazine and pulmonary artery balloon and right atrial catheters inserted. More xylazine was administered prior to anesthetic induction with ketamine and propofol IV. Anesthesia was maintained for 60 minutes (or until surgery was complete) using either propofol IV infusion or isoflurane to effect. All horses were administered dexmedetomidine and ketamine infusions IV, and IV butorphanol. The endotracheal tube was attached to a large animal circle system and the lungs were ventilated with oxygen to maintain end-tidal CO₂ 40 ± 5 mmHg. Measurements of cardiac output, heart rate, pulmonary arterial and right atrial pressures, and body temperature were made under xylazine sedation. These, arterial and venous blood gas analyses were repeated 10, 30 and 60 minutes after induction. Systemic arterial blood pressures, expired and inspired gas concentrations were measured at 10, 20, 30, 40, 50 and 60 minutes after induction. Horses were recovered from anesthesia with IV romifidine. Times to extubation, sternal recumbency and standing were recorded. Data were analyzed using one and two-way anovas for repeated measures and paired t-tests. Significance was taken at p=0.05.ResultsPulmonary arterial and right atrial pressures, and body temperature decreased from pre-induction values in both groups. PaO₂ and arterial pH were lower in propofol-anesthetized horses compared to isoflurane-anesthetized horses. The lowest PaO₂ values (70–80 mmHg) occurred 10 minutes after induction in two propofol-anesthetized horses. Cardiac output decreased in isoflurane-anesthetized horses 10 minutes after induction. End-tidal isoflurane concentration ranged 0.5%–1.3%.Conclusion and clinical relevanceBoth anesthetic protocols were suitable for arthroscopy. Administration of oxygen and ability to ventilate lungs is necessary for propofol-based anesthesia.     

Effect of preoperative administration of tepoxalin on induction dose of injectable anesthetics in dogs

Medications given preoperatively have the potential to affect the induction dose of injectable anesthetics, which could result in an anesthetic overdose. Tepoxalin is an NSAID approved for the treatment of arthritis in dogs in the United States and hence could be administered in patients requiring anesthesia. In this study, administration of a single dose or a 10-day course of tepoxalin did not affect the induction dose (dose that allowed intubation) of propofol, thiopental, or ketamine-diazepam and also did not affect the time required for dogs to recover from anesthesia.     

Effects of dissociative anesthesia opioid-free protocols combined with local anesthesia,with or without flumazenil or atipamezole postoperatively,for orchiectomy in cats

ObjectiveTo evaluate the anesthetic effects of two drug combinations with local anesthesia, with or without postoperative antagonists, for orchiectomy in cats.Study designProspective, randomized blinded clinical study.AnimalsA total of 64 healthy cats.MethodsCats were assigned to four equal groups: ketamine (5 mg kg^–1) and dexmedetomidine (10 μg kg^–1) were administered intramuscularly (IM), followed postoperatively with intravenous (IV) saline (5 mL; group KDS) or atipamezole (50 μg kg^–1; group KDA); and ketamine (14 mg kg^–1) with midazolam (0.5 mg kg^–1) and acepromazine (0.1 mg kg^–1) IM, with postoperative IV saline (5 mL; group KMAS) or flumazenil (0.1 mg kg^–1; group KMAF). Lidocaine (2 mg kg^–1) was divided between subcutaneous and intratesticular injection. Physiologic variables were recorded at time points during anesthesia. Ketamine rescue dose was recorded. The degree of sedation and the quality of recovery were evaluated postoperatively.ResultsTime to loss of pedal reflex was longer in groups KMAS and KMAF than in groups KDS and KDA (p = 0.010). Total rescue dose of ketamine was higher in KMAS and KMAF than in KDS and KDA (p = 0.003). Heart rate (HR) during anesthesia was higher in KMAS and KMAF than in KDS and KDA (p = 0.001). Times to head up (p = 0.0005) and to sternal recumbency (p = 0.0003) were shorter in KDA than in KDS, KMAS and KMAF. Lower sedation scores were assigned sooner to KDA than KDS, KMAS and KMAF (p < 0.001). Recovery quality scores were good in all groups.Conclusions and clinical relevanceBoth anesthetic protocols allowed the performance of orchiectomy. Groups KMAS and KMAF required higher rescue doses of ketamine before injecting lidocaine. HR and oscillometric systolic pressure were minimally changed in groups KD and tachycardia was recorded in groups KMA. Only atipamezole shortened the anesthetic recovery.     

A multisite case report on the clinical use of sevoflurane in dogs

The purpose of this report was to evaluate the clinical safety and efficacy of sevoflurane as an inhalant anesthetic in dogs. Subjective and objective data from 196 clinical cases utilizing sevoflurane as the maintenance anesthetic was collected at three sites. After preanesthetic evaluation, the attending anesthesiologist assigned the dogs to one of the following six anesthetic protocols: protocol 1, oxymorphone premedication and thiopental induction; protocol 2, oxymorphone/acetylpromazine premedication and thiopental induction; protocol 3, xylazine/butorphanol premedication and thiopental induction; protocol 4, opioid premedication and propofol induction; protocol 5, optional premedication and mask induction with sevoflurane in oxygen; and protocol 6, optional premedication and optional induction. The average quality of induction, maintenance, and recovery was good to excellent in all protocols. The three most common side effects during maintenance and recovery were hypotension, tachypnea, and apnea. Sevoflurane produces anesthesia in dogs comparable to the other inhalation anesthetics currently used (i.e., halothane and isoflurane) for diagnostic or therapeutic procedures.     

Assessment of cardiac troponin I and C-reactive protein concentrations associated with anesthetic protocols using sevoflurane or a combination of fentanyl, midazolam, and sevoflurane in dogs

ObjectiveTo report serum cardiac troponin I (cTnI) and C-reactive protein (CRP) concentrations in dogs anesthetized for elective surgery using two anesthetic protocols.Study designProspective, randomized clinical study.AnimalsTwenty client-owned dogs presenting for elective ovariohysterectomy or castration.MethodsThe dogs were randomized into two groups. All dogs were premedicated with glycopyrrolate (0.011 mg kg^?1) and hydromorphone (0.1 mg kg^?1) IM approximately 30 minutes prior to induction of anesthesia. Anesthesia in dogs in group 1 was induced with propofol (6 mg kg^?1) IV to effect and in dogs in group 2 with diazepam (0.2 mg kg^?1) IV followed by etomidate (2 mg kg^?1) IV to effect. For maintenance of anesthesia, group 1 received sevoflurane (adjustable vaporizer setting 0.5–4%) and group 2 received a combination of fentanyl (0.8 μg kg^?1 minute^?1) and midazolam (8.0 μg kg^?1 minute^?1) IV plus sevoflurane (adjustable vaporizer setting 0.5–4%) to maintain anesthesia. Serum cTnI and CRP concentrations were measured at baseline and 6, 18, and 24 hours post-anesthetic induction. Biochemical analysis was performed at baseline. Lactate was obtained at baseline and 6 hours post-anesthetic induction. Heart rate and mean arterial blood pressure were measured intra-operatively.ResultsBaseline serum cTnI and CRP concentrations were comparable between groups. A significant difference in serum cTnI or CRP concentrations was not detected post-operatively between groups at any time point. Serum CRP concentrations were significantly increased post-anesthetic induction in both groups, which was attributed to surgical trauma.Conclusions and clinical relevanceThere was no significant difference in serum cTnI and CRP concentrations between anesthetic protocols. Further investigation in a larger number of dogs is necessary to confirm the current findings.     

Perioperative use of selective alpha-2 agonists and antagonists in small animals

Alpha-2 agonists are the only single class of anesthetic drugs that induce reliable, dose-dependent sedation, analgesia, and muscle relaxation in dogs and cats. Used at low doses, as adjuncts to injectable and inhalational anesthetics, selective alpha-2 agonists dramatically reduce the amount of anesthetic drug required to induce and maintain anesthesia. This reduction in anesthetic requirements is achieved without significant depression of pulmonary function and with limited effects on cardiovascular function. Selective alpha-2 agonists can also be used postoperatively to potentiate the analgesic effects of opioids and other drugs. Given the nearly ideal pharmacodynamic profile and reversibility of alpha-2 agonists, these drugs will play a central role in balanced approaches to anesthesia and the management of perioperative pain in healthy dogs and cats.     

Evaluation of bupivacaine liposome injectable suspension efficacy in single-use vials over five days of multiple use

ObjectiveTo test the anesthetic effect of a bupivacaine liposome injectable suspension (BLIS), used in a multiple-dose manner for up to 5 consecutive days.Study designProspective, randomized, experimental study.AnimalsA total of 30 male and female Sprague–Dawley rats (Rattus norvegicus), aged 97 (75–130) days and weighing 337.2 (219.6–465.9) g, mean (range).MethodsRats were assigned to one of five BLIS vial groups, in which drug was administered from a newly opened vial or 1, 2, 3 and 4 days after the vial was opened. The vials were refrigerated between uses. A 14 gauge needle attached to an injection plug was used to puncture each vial once and was not removed; BLIS was withdrawn from the injection plug in a multiple-dose fashion. A dose rate of 0.4 mL kg⁻¹ was administered subcutaneously into the left pelvic limb paw. Antinociception was evaluated using a paw pressure test on both injected and uninjected paws before (time 0, baseline) and 1, 24, 48 and 72 hours after injection.ResultsAge of BLIS vial had no significant effect on anesthetic efficacy (p = 0.97). Across all groups, paw withdrawal latency averaged 5.23 ± 0.24 seconds at baseline (before BLIS injection), increased to 16.45 ± 0.65 seconds at 1 hour after BLIS injection, declined to 7.50 ± 0.76 seconds at 24 hours after BLIS injection, and further declined thereafter (p < 0.001). There was no significant change in paw withdrawal latency in the uninjected paw over time.Conclusions and clinical relevanceBLIS single-use vials retained efficacy when used up to 5 days in a multiple-dose fashion. Because anesthetic effects declined substantially after 24 hours, multimodal pain management remains important for providing analgesia care.     

Naltrexone does not affect isoflurane minimum alveolar concentration in cats

ObjectiveTo test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids.Study designRandomized, crossover, placebo-controlled, blinded experimental design.AnimalsSix healthy adult cats weighing 4.9 ± 0.7 kg.MethodsThe cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg^?1 naltrexone) was administered IV every 40–60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later.ResultsIsoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration.Conclusion and clinical relevanceMinimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.     

Results of the confidential enquiry into perioperative small animal fatalities regarding risk factors for anesthetic-related death in dogs

OBJECTIVE: To identify major risk factors associated with anesthetic-related death in dogs. DESIGN: Case-control study. ANIMALS: 148 dogs that died or were euthanized within 48 hours after undergoing anesthesia or sedation and for which anesthesia could not be reasonably excluded as a contributory factor (cases) and 487 control dogs that did not die within 48 hours after undergoing anesthesia or sedation (controls). PROCEDURES: Details of patient characteristics, preoperative evaluation and preparation, procedure, anesthetic and sedative agents used, monitoring, postoperative management, and personnel involved were recorded. Mixed-effects logistic regression modeling was used to identify factors associated with anesthetic-related death. RESULTS: An increase in physical status grade, urgency of the procedure, age, or intended duration of the procedure; a decrease in body weight; anesthesia for a major versus a minor procedure; and use of injectable agents for anesthetic induction and halothane for maintenance or use of inhalant anesthetics alone (compared with use of injectable agents for induction and isoflurane for maintenance) were associated with increased odds of anesthetic-related death. CONCLUSIONS AND CLINICAL RELEVANCE: The results suggested that specific factors could be associated with increased odds of anesthetic-related death in dogs. Knowledge of these factors should aid the preoperative assessment and perioperative management of dogs undergoing anesthesia and sedation.     

Prevalence and risk factors for canine post‐anesthetic aspiration pneumonia (1999–2009): a multicenter study

ObjectiveTo determine the incidence of canine post-anesthetic aspiration pneumonia (AP) and to identify anesthetic agents, procedures and management factors associated with the development of AP.Study designMulticenter, randomized, case-controlled retrospective study.AnimalsTwo hundred and forty dogs affected with AP and 488 unaffected control dogs.MethodsElectronic medical record databases at six Veterinary colleges were searched for dogs, coded for anesthesia or sedation and pneumonia from January 1999 to December 2009. The resultant 2158 records were hand-searched to determine eligibility for inclusion. Diagnosis of AP was made radiographically. Two unaffected control dogs were randomly selected for each affected dog, from a list of dogs that underwent sedation or anesthesia in the same time period and did not develop aspiration pneumonia. Fifty-seven factors were then evaluated for association with aspiration pneumonia. Data analysis was performed using univariate Chi-square or student t-tests, then multivariate logistic regression.ResultsIncidence of post-anesthetic AP was 0.17%, from 140,711 cases anesthetized or sedated over the 10 year period. Two anesthesia-related events were significantly associated with development of AP: regurgitation and administration of hydromorphone at induction. Administration of anticholinergics was not associated with AP. Procedures associated with increased odds of aspiration pneumonia included laparotomy, upper airway surgery, neurosurgery, thoracotomy and endoscopy. Orthopedic surgery, ophthalmologic surgery, dental procedures, MRI, CT, bronchoscopy, cystoscopy, tracheoscopy and neutering were not associated with development of AP. Three patient factors were associated with the development of AP: megaesophagus, and a history of pre-existing respiratory or neurologic disease. Sixty-nine% of dogs with two or more of the above independent predictive variables developed AP.Conclusion and clinical relevanceMost anesthetic agents and procedures were not associated with the development of AP. We need to devise and evaluate strategies to protect at risk patients.