The aim was to assess and identify species-specific risks and risk factors for anaestheticrelated death in small animals in the UK. In this study, in which 117 centres participated, general anaesthetics and sedations of 98,036 dogs, 79,178 cats, and 8,209 rabbits were evaluated.

In total, 163 dogs, 189 cats and 114 rabbits suffered from anaestheticrelated deaths. Recovery from anaesthesia proved to be the period with the highest risk – 50% of dog deaths and 60% of cat deaths occurred during this phase (Brodbelt, 2006). These figures prove it is extremely important the level of consciousness and clinical parameters of the patient are carefully and regularly assessed, not only during anaesthesia itself, but also during recovery.

Deterioration of vital parameters, blunted responsiveness, delayed awakening or failure to awaken following anaesthesia must be recognised quickly, diagnosed accurately and responded to appropriately. In case of a delayed recovery, one must determine whether it is a normal recovery for this patient or a pathological delay that should be addressed.

The time to emerge to full consciousness is affected by a number of factors, which may include:

• drugs used perioperatively – drugs with a long duration of action may delay return to consciousness;
• duration of anaesthesia – long anaesthetics are associated with a greater risk of drug accumulation, and an increased risk of hypothermia, hypoglycaemia, hypotension and hypoxaemia, which are all factors influencing recovery (Holden, 2007); and
• concurrent disease – hepatic, renal and/or thyroid dysfunction all may delay metabolism and/or clearance of anaesthetics agents.

Drug-related causes

The residual effects of a drug are influenced by many variables and, therefore, it is not surprising administration of an “ideal” dose to one patient can have a very different effect on another, apparently similar, patient. So, it is important to treat each animal as an individual patient, and to tailor drugs to the desired effect instead of using standardised doses.

Sedatives

Commonly used sedatives in veterinary practice are acepromazine, α2-adrenoceptor agonists and benzodiazepines, although the latter two are not licensed in the UK.

The author tends to use relatively low doses of both acepromazine and α2-adrenoceptor agonists for sedation and pre-anaesthetic medication. Acepromazine may be administered at doses of 5µg/ kg to 20ìg/kg intravenously, or 10µg/kg to 30µg/kg intramuscularly; medetomidine at 1µg/ kg to 2µg/kg intravenously and between 2µg/kg to 10µg/kg intramuscularly (see ^{Table 1}).

The larger the patient, the lower the dose of sedative drugs required. Clinical doses of acepromazine given to large breed dogs may result in prolonged recovery compared to small breeds, which is related to the higher metabolic rate in small animals. The author tends to not give more than 1.0mg of acepromazine regardless of the size of the patient – higher doses do not result in better sedation, but do aggravate potential side effects such as hypotension, reflex tachycardia and prolonged recovery.

Benzodiazepines (midazolam, diazepam) used alone are relatively short-acting, although their resultant central nervous system depression can prolong the effect of other anaesthetic agents. Due to its poor water solubility, diazepam is either formulated as an emulsion or formulated with propylene glycol.

Both preparations are not suitable for intramuscular injection because of either poor absorption or tissue damage (propylene glycol). However, midazolam is water soluble and can therefore be injected intramuscularly. High doses of α2-adrenoceptor agonists may produce a profound and relatively long sedation that is dose-dependent, but prompt recovery can be achieved by the administration of an α2-antagonist (atipamezole).

Opioids

Opioids produce analgesia, sedation and may cause respiratory depression, but this is rare in veterinary patients. The animal’s response to a given dose may be affected by the co-administration of other sedatives and analgesics, as well as by patient factors. For example, methadone (unlicensed in cats) has been shown to increase the sedative effects of acepromazine (synergism) in dogs (Monteiro, 2009).

Intravenous agents

The duration of effect of most intravenous agents given as a single bolus for induction of anaesthesia depends on redistribution. Therefore, single use of such agents should not delay recovery. On the other hand, propofol administered as part of a total intravenous anaesthesia (TIVA) regime may have a prolonged effect; recovery time is dependent on the duration and rate of the infusion (Andreoni, 2009).

Cats in particular, which lack the glucuronyl transferase enzyme necessary for metabolism of phenolic compounds like propofol, are prone to accumulation of this drug (Pascoe, 2006).

Volatile anaesthetic agents

Emergence from inhalational anaesthesia depends on pulmonary elimination of the volatile agent. Pulmonary elimination is determined by alveolar ventilation, pulmonary circulation, the solubility of the agent and the duration of its administration. Generally, the use of inhalant agents with low solubility in blood and tissues results in faster induction and recovery times.

Clinically, patients seem to recover quicker from sevoflurane (licensed in dogs), which has a lower blood solubility than isoflurane anaesthesia. This has also been proven by Lopez et al (2009) under research conditions. However, Jimenez et al (2009) did not find any significant difference between the two agents under clinical conditions.

Metabolic causes

Hypoglycaemia

The brain is solely dependent on glucose as its energy source. Neuroglycopenia manifests as confusion, abnormal behaviour, seizures and eventually coma. Hypoglycaemia can be clinically silent in anaesthetised patients, which emphasises the importance of glucose monitoring in susceptible patients such as neonates, juvenile patients (especially toy breeds) and diabetic patients who have been starved (Chelliah, 2000; Koenig, 2009).

Concurrent/underlying diseases

Electrolyte imbalances and other (undiagnosed) metabolic disorders can lead to prolonged recoveries. Both hyponatraemia and hypernatraemia may cause confusion, drowsiness and, eventually, coma. This must be taken into account in case inappropriate fluid therapy occurred during the anaesthetic period, the patient has been on long-term fluid treatment or suffers from underlying disease resulting in electrolyte abnormalities. Liver disease (^{Figure 1}) and hypothyroidism may decrease the rate of metabolism of anaesthetic drugs, prolong the duration of their effect and, therefore, the time to recover from anaesthesia. Care must be taken in patients with decreased liver metabolism and it is suggested to use:

• lower doses compared to healthy patients
• drugs (partly) relying on extrahepatic metabolism (propofol instead of thiopental for induction, atracurium instead of vecuronium for neuromuscular blockade – the latter two are not licensed)
• short-acting drugs
• drugs that can be antagonised (α2-adrenoceptor agonists, morphine or methadone)

Kidney disease may result in accumulation of drugs of which the clearance is renal-dependent (for example, ketamine). This has to be kept in mind in, for instance, geriatric patients in which renal function may be sub-optimal.

Adverse perioperative events

Hypoventilation

Reduced minute volume results in hypercapnia, which is defined as arterial carbon dioxide levels above 45mmHg. Potential causes of hypoventilation may include residual effects of anaesthetic agents, hypothermia, neuromuscular disorders and space-occupying lesions within the chest. Pain, for instance, after thoracotomy or due to rib fractures, may be an important contributing factor to hypoventilation, as it may limit chest excursions.

Hypercapnia associated with respiratory depression may cause severe mental impair ment and may even result in respiratory arrest. Hypoventilation results not only in hypercapnia, but possibly hypoxaemia when the patient is breathing room air, as alveolar oxygen partial pressure may be reduced by the increased alveolar carbon dioxide partial pressure.

The use of capnometry during the anaesthetic and recovery period (capnograph connected either to the endotracheal-tube or by using nasal prongs once the patient is extubated) facilitates detection and early correction of respiratory depression (Bednarski, 2007).

Hypoxaemia

Young and healthy animals undergoing routine procedures usually do not need supplemental oxygen during recovery. Hypoxaemia is defined as an arterial oxygen tension below 60mmHg, corresponding to pulse oximeter readings of 90% and lower.

Most common causes of hypoxaemia are decreased fraction of inspired oxygen during anaesthesia (concomitant use of nitrous oxide), diffusion hypoxaemia when insufficient time is allowed to washout nitrous oxide before disconnecting the patient from the breathing system, hypoventilation, upper airway obstruction and atelectasis-related ventilation/ perfusion mismatch.

Cyanotic mucous membranes are a late sign of hypoxaemia (^{Figure 2}), and may also be masked by anaemia. For these reasons, the use of pulse oximetry is strongly recommended to monitor the saturation status of the patient in the early phases of the recovery period. Often, hypoxaemia can be easily addressed if detected early.

Sick or debilitated animals, such as anaemic or respiratory-compromised patients, may benefit from supplemental oxygen during recovery, particularly if they are hypothermic, as shivering can easily increase oxygen consumption by 200%.

Hypothermia

This occurs commonly in anaesthetised patients and may be the result of:

• the depressant effects of anaesthetic agents on thermoregulation
• vasodilation resulting in excessive heat loss relative to metabolic production
• muscle inactivity
• loss of heat due to convection, radiation and conduction; especially if the patient is in contact with cold surfaces

The more hypothermic the patient becomes, the higher the risk of neurological and cardiovascular changes. In humans, confusion is likely to happen at body temperatures below 35ºC, unconsciousness below 30ºC and absent cerebral activity below 18ºC. At a body temperature of 36ºC, cardiovascular and respiratory effects such as bradycardia, arrhythmias and hypoventilation may already be seen, together with delayed drug metabolism (Murison, 2001).

Hypotension

Hypotension associated with blood loss, poor cardiac function and/or vasodilation may cause alteration in mentation and may result in slow recoveries. It is good practice to periodically measure blood pressure in debilitated patients during the recovery period.

What to do?

Many problems resulting in delayed recoveries from anaesthesia can be prevented with appropriate patient monitoring during and after anaesthetic drug delivery. The following steps are suggested as a guideline for the management of patients that do not recover from anaesthesia within the expected time frame:

• Check patency of the airways and the respiratory function of the patient (^{Figure 3}):
• Respiratory rate and chest excursion are useful to evaluate if ventilation is adequate or if respiratory depression due to anaesthetic drugs is present. If respiration is stertorous with increased upper respiratory sounds, open the mouth and pull out the tongue. The neck may be stretched forward and the back of the head can be positioned slightly elevated compared to the nose. An increased respiratory effort that may be associated with paradoxical breathing could be a sign of airway obstruction. If the patient struggles to ventilate and cannot control its own airways, it may be wise to re-intubate.
• Ensure that appropriate oxygenation is present by the use of pulse oximetry (^{Figure 4}). If hypoxia is suspected (SpO₂ < 90%), supplemental oxygen is mandatory (^{Figure 5}). Consider reversing drugs used that could cause respiratory depression, bearing in mind that antagonising opioids and α2-adrenergic agents results in reversing their analgesic properties. Arterial blood gas analysis is very useful in assessing pulmonary function status of the patient, but, unfortunately, not always practical and possible.
• Check oxygenation status and cardiovascular function. Assess pulse rate and quality (ideally at a peripheral artery; ^{Figure 6}), mucous membranes’ colour and capillary refill time. Intravenous fluid support should be given if there are signs of hypotension or underperfusion.
• Check body temperature. If the patient is cold, active warming must be started and continued until the patient has regained normal body temperature and motor function.
• Check for signs of pain and provide analgesia if necessary. For instance, cranial abdominal and thoracic pain may result in hypoventilation, which may reduce the elimination of volatile agents.
• If an intravenous catheter is in place, it’s useful to ensure its patency until the animal is fully awake and recovered.
• Collect a blood sample to measure packed cell volume, total proteins, electrolytes and glucose, to rule out potential causes, such as haemorrhage, anaemia, electrolytes imbalances and hypoglycaemia (Holden, 2007).
• Until the patient is recovered from anaesthesia, monitoring vital parameters and providing respiratory, cardiovascular and thermal support where needed is of paramount importance.
• This article, which mentions some treatments not licensed for veterinary or species use, has been reviewed by Marieke De Vries, clinical anaesthetist at the AHT.