Intracranial Disease: Anaesthesia, Analgesia and Supportive Care

Anaesthesia

Considerations for anaesthetizing animals with intracranial disease are summarized in Table Considerations for anaesthetizing animals with intracranial disease (CNS = central nervous system; cerebral pertusion pressure = cerebral perfusion pressure; ICP = intracranial pressure; MABP = mean arterial blood pressure)

Problem Aetiology Anaesthetic management
Decreased CPP Decreased MABP Increased ICP Maintain MABP at 80-100 mmHg

Maintain normovolaemia

Drugs that minimally depress cardiovascular function

Haemodynamic instability Sympathetic stimulation:

Stress, struggling

Intubation and extubation

Surgical stimulus

Reduce sympathetic stimulation:

Excitement-free induction

Minimize pressor response to intubation/extubation

Provide analgesia

Hypoventilation Brainstem disease or forebrain disease with compression of brainstem Pre-oxygenate

Monitor adequacy of ventilation

Provide assisted/mechanical ventilation when necessary

Seizure activity Forebrain disease Avoid agents that decrease seizure threshold or that are epileptogenic
Aspiration pneumonia Brainstem disease: cranial nerve deficits cause decreased laryngeal reflexes, dysphagia and megaoesophagus Rapid intubation and control of airway

Consider feeding by gastrostomy tube

Fluid and electrolyte abnormalities Dehydration: decreased food and water intake

Diseases of pituitary/hypothalamus: Cushing’s, diabetes insipidus, inappropriate salt wasting

Polyuria associated with chronic corticosteroid administration increases risk of dehydration

Correct fluid and electrolyte imbalances prior to anaesthesia
Alteration in drug pharmacokinetics Phenobarbital administration:

Competes with protein-bound drugs

Induces cytochrome P450 enzyme metabolism

Decrease dose of drugs that exhibit high protein binding

Increase frequency of administration of drugs metabolized by cytochrome P450

Alteration in drug pharmacodynamics CNS pathology

Phenobarbital administration

Exacerbation of the CNS depressant effects of anaesthetic agents requires careful administration + dose reduction

Sedation

Heavy sedation can be used in healthy animals to allow diagnostic tests such as radiography and ultrasono-graphy to be performed. In animals with clinical signs of intracranial disease, heavy sedation is generally avoided as this may lead to hypoventilation and associated increases in ICP. In addition, heavy sedation will interfere with the accurate assessment of the neurological status of the animal and thus may delay the instigation of appropriate therapy. In these cases anaesthesia is preferable, as it allows the airway to be protected and ventilation to be controlled. In addition, many anaesthetic agents, such as propofol and barbiturates, have the added benefit of reducing the cerebral metabolic rate, which helps to reduce neurological injury in these animals.

Premedication

Premedication is generally limited to an analgesic agent unless the animal is particularly anxious. When anxiolysis is required, the choice of agents is somewhat controversial. Characteristics of agents used for sedation or premedication are listed in Table Characteristics of intravenous sedatives and induction agents used in animals and recommendations for use in animals with central nervous system disease (Commonly used dose rates are also provided. cerebral blood flow = cerebral blood flow; CMR = cerebral metabolic rate; CV = cardiovascular; ICP = intracranial pressure; NR = not reported; VC = vasoconstriction; VD = vasodilation)

Agent CBF

regulation

Direct CV effects CMR ICP Seizure activity Comments Dose
Acepromazine maieate NR Arterial VD and hypotension NR NR Avoid in intracranial disease

Useful anxiolytic

Ensure normovolaemia

0.01-0.02 mg/kg i.m.
Alpha-2 agonists Row-metabolism coupling ↓ Initial arterial VC with hypertension

Arterial VD and hypotension

No effect Avoid in intracranial disease

Useful in fractious animals

Ensure normovolaemia

Medetomidine:

Dogs: 2-10 ug/kg i.m.

Cats: 5-20 ug/kg i.m.

Opioids Normal Bradycardia

Hypotension with rapid bolus

Reduce dose of induction and maintenance agents Drug action – reduces response to intubation and surgical stimulus See Table
Benzodiazepines Normal No direct vascular effects ↓↓ Possible sedative/anxiolytic

Reduce induction agent dose

Drug action – potentiates respiratory depression of other agents

Diazepam 0.1-0.2 mg/kg i.v.

Midazolam0.1-0.2 mg/kg i.v./i.m.

Lidocaine Normal Myocardial depression

Hypotension

Low dose ↓ High dose ↑ Drug action – reduces response to intubation and extubation 1 mg/kg i.v.
Thiopental Normal Myocardial depression

Arterial VD

Hypotension

↓↓ ↓↓ Drug action -may cause excitement in unsedated animals

Accumulates with repeated dosing

Induction: up to 10 mg/kg i.v.
Propofol Normal Myocardial depression

Arterial VD

Hypotension

↓↓ ↓↓ Excitement-free induction

Suitable for maintenance of anaesthesia in dogs with intracranial disease

Induction: up to 2-4 mg/kg i.v.

Maintenance: 0.2-0.4 ug/kg/min

Ketamine Normal Arterial VC

Tachycardia

Hypertension

↑↑ Avoid in intracranial disease

Avoid in animal at risk of seizures (myelography)

1-2 mg/kg i.v.

Acepromazine maieate (ACP) is an anxiolytic commonly used in healthy animals. As this agent is reported to decrease seizure threshold, it has been recommended that it should not be used in animals that are at risk of seizures (). Benzodiazepines, such as diazepam or midazolam, may be useful as anxiolytics in patients with intracranial disease. However, it must be remembered that the effects of benzodiazepines in small animals can be unpredictable and that excitement, dysphoria and disinhibition can occur (Court etal., 1990a). Thus, the use of these agents in animals with CNS disease should be undertaken with caution. Alpha-2 agonists, such as medetomidine, can produce marked sedation and significant cardiopulmonary dysfunction even when administered at low doses () and are best avoided in animals with intracranial disease. Administration of phenobarbital at 2-3 mg/kg i.m. is a useful premedication in some anxious dogs, when administered in conjunction with methadone.

Induction

Anaesthesia is induced using intravenous agents () in order to provide a smooth induction with minimal struggling and rapid control of the airway.

Propofol is the agent most frequently used in animals with intracranial disease. It can be administered slowly to effect in minimally sedated animals without excitement. An additional advantage of propofol is that a single induction dose is metabolized more rapidly than thiopental, resulting in a more complete recovery.

Pre-oxygenation for 5-10 minutes and delivery of oxygen during induction are recommended to prevent hypoxaemia. Manual ventilation with a close-fitting mask during induction and rapid intubation can help to prevent hypercapnia.

Intubation and extubation are potent stimulators of the sympathetic nervous system. Resultant increases in heart rate and blood pressure can have marked effects on ICP. Pressor response associated with intubation can be minimized by administration of potent opioids (e.g. fentanyl), lidocaine or short-acting beta blockers such as esmolol. Bolus administration of potent opioids such as fentanyl (2-5 ug/kg i.v.) can cause significant bradycardia, hypotension and associated decreases in cerebral perfusion and marked respiratory depression. Ventilation is mandatory as soon as intubation is achieved in order to prevent hypercapnia and associated increases in ICP. Lidocaine administered at 1 mg/kg i.v. immediately priorto the induction agent has been used to obtund pressor response to intubation in dogs () but the efficacy of this agent has not been fully ascertained. Cats have increased sensitivity to parenteral lidocaine and in this species topical application on the larynx is preferred.

Maintenance

Inhalation agents are still commonly used for maintenance of anaesthesia in animals with intracranial disease. Total intravenous anaesthesia is the preferred method during intracranial surgery in dogs.

The detrimental effects of volatile agents (Table: Characteristics of inhalation agents used in animals and recommendations for use in animals with central nervous system disease) can be minimized by using concurrent administration of potent opioids to reduce the dose of volatile agent used. Ventilating these animals to normocapnia also reduces detrimental effects of inhalation agents.

Table: Characteristics of inhalation agents used in animals and recommendations for use in animals with central nervous system disease (BP = blood pressure; cerebral blood flow = cerebral blood flow; CMR = cerebral metabolic rate; CV = cardiovascular; ET% = end tidal percentage; ICP = intracranial pressure; IPPV = intermittent positive pressure ventilation)

Agent CBF regulation Direct CV effects CMR ICP Seizures Comments
Enflurane Autoregulation ↓

Flow-metabolism coupling ↓

Chemical regulation ↓

Cerebral vasodilation

Systemic BP ↓↓

↓ (low ET%)

↑ (high ET%)

↑↑ Avoid in neurological patients
Halothane Autoregulation ↓↓

Flow-metabolism coupling ↓

Chemical regulation ↓

Cerebral vasodilation

Systemic BP ↓↓

↑↑↑ Avoid in neurological patients
Isoflurane Autoregulation ↓ Flow-metabolism coupling ↓

Chemical regulation: normal

Cerebral vasodilation

Systemic BP ↓↓

Useful in neurological patients IPPV required to decrease detrimental effects on CBF
Sevoflurane Autoregulation ↓

Flow-metabolism coupling ↓

Chemical regulation: normal

Cerebral vasodilation

Systemic BP ↓↓

Useful in neurological patients IPPV required to decrease detrimental effects on CBF
Nitrous oxide Not reported Potent cerebral vasodilator Minimal systemic effects No effect ↑ (potentiates other volatile agents) No effect Avoid in patients with increased ICP

Total intravenous anaesthesia consists of continuous-rate infusions of propofol and potent opioids such as alfentanil or remifentanil. It is currently the preferred method in human neurosurgery and has recently been reported in canine neurosurgical patients (). Due to slower metabolism of propofol in cats, accumulation and prolonged recoveries are likely. As a

result, inhalation anaesthesia with isoflurane or sevoflurane is still the preferred technique for use in cats. A technique using a combination of sevoflurane and alfentanil has been described for craniectomies in cats ().

The rationale for use of total intravenous anaesthesia in dogs is based on the beneficial effects of propofol on cerebral perfusion () and its pharmacokinetics, which allow propofol to be administered by continuous infusion without accumulation and prolonged recovery. Concurrent infusion of opioids such as alfentanil and remifentanil () is used to decrease the dose of propofol and thus reduce the effects of propofol on systemic cardiovascular function. In addition, continuous infusions of opioids help to minimize sympathetic stimulation and haemo-dynamic responses to surgery, which can have detrimental effects on cerebral blood flow and ICP.

Patient position

Positioning of the patient during surgery is important. It is essential to ensure that jugular veins are not occluded. Head elevation is also recommended, to help decrease ICP.

Monitoring

Ventilation:

IPPV is essential during anaesthesia of animals with intracranial disease, to ensure normocapnia (PaCO2 at 35-45 mmHg).

Adequacy of ventilation can be assessed using capnography but blood gas analysis is preferred during neurosurgery ().

Cardiovascular function:

Monitoring arterial blood pressure is important in order to ensure that adequate MABP and cerebral pertusion pressure are maintained. Monitoring CVP is important in order to ensure that venous return is not impaired and that hydration is adequate.

Forintracranial surgical procedures, invasive monitoring of arterial blood pressure (ABP) and CVP is recommended. To ensure adequate cerebral pertusion pressure in patients with increased ICP, it is recommended that MABP is maintained between 80 and 100 mmHg. CVP in animals breathing spontaneously should normally be between 0 and 4 mmHg. IPPV will increase the mean CVP due to the increase in mean intrathoracic pressure. It is not unusual to observe CVP up to 8 mmHg in ventilated animals. High CVP (>10 mmHg) may indicate overhydration, decreased cardiac function or excessive pressures used for ventilation.

Pulmonary function:

Monitoring pulmonary function is essential in order to ensure normocapnia (PaCO2 at 35-45 mmHg) and adequate oxygenation (PaO2 >80 mmHg). Capnography and pulse oximetry can be used as a guide to adequacy of pulmonary function. In critically ill animals or during intracranial surgery, direct measurement of arterial blood gases is recommended.

Capnography: This can be used to assess adequacy of ventilation. This technique measures CO2 in the expired patient gases (PETCO2), which is equivalent to CO2 tension in the alveoli (Pa/vCO2). As alveolar gases are in equilibrium with arterial blood, PETCO2 can be used to approximate PaCO2. In patients with cardiovascular (CV) compromise, PaCO2 may differ from PETCO2 by as much as 10-20 mmHg, due to presence of physiological dead space. For short anaesthetic procedures, such as for diagnostic imaging or CSF sampling, capnography is adequate for monitoring ventilation and IPPV is generally adjusted to achieve a PETCO2 of 30-35 mmHg. For longer procedures such as surgery, direct analysis of arterial blood gases is essential.

Pulse oximetry: This can be used to provide a guide to the oxygenation of the patient. This technique measures the percentage of haemoglobin (Hb) that is saturated with oxygen. Due to the shape of the oxygen dissociation curve, a saturation of >95% is required to ensure a PaO2 >80 mmHg (). There are many physiological and technical factors that can interfere with pulse oximetry. Detailed discussion of these factors and of the oxygen-carrying capacity of blood is beyond the scope of this chapter but can be found in West (2000). Where possible, arterial blood gas analysis should be performed. It is important to note that pulse oximetry does not assess adequacy of ventilation and that severe hypercapnia can develop despite adequate oxygen saturation.

Body temperature: Body temperature in animals with CNS disease should be maintained within the normal range ().

• Hypothermia decreases cerebral metabolic rate (CMR) and has been used in human patients as a form of neuroprotection. However, the efficacy of controlled hypothermia has been a contentious issue, due to its inconsistent effect on outcome (). Furthermore, hypothermia leads to shivering and increased oxygen consumption during recovery, and should be avoided.

• Hyperthermia increases CMR, which increases cerebral blood flow and can lead to increases in ICP and further reductions in CPP.

It is important to remember that head trauma and intracranial surgery in animals, especially involving the brainstem and hypothalamus, can result in impaired thermoregulation. Close monitoring of temperature in these animals is imperative, and instigation of appropriate therapy should be performed when abnormalities arise. Methods for supporting body temperature are discussed in more detail below.

Recovery

The aim of recovery is to achieve a smooth emergence with minimal coughing and straining. Timing of extubation of animals with intracranial disease is a compromise between ensuring that the animal is able to ventilate adequately and maintain normocapnia while preventing a pressor response and coughing.

To minimize the pressor response the same techniques can be used as those described for intubation. Lidocaine administered at a dose of 1 mg/kg i.v. can be useful a few minutes prior to extubation. Hypertension (MABP >130 mmHg; SABP >160-200 mmHg) in the recovery period can be treated by administration of beta-receptor antagonists. Esmolol is the agent of choice, due to its short duration of action which allows it to be titrated to effect. This agent has been used to blunt pressor response to extubation in humans and is reported to be more effective than other beta blockers (). The use of esmolol in small animal neurosurgical patients has not been reported. Dose rates used in cardiovascular disease in dogs and cats include 0.25-0.5 mg/kg by slow intravenous injection or 10-200 ug/kg/minute infusion titrated to effect.

Analgesia

Intracranial disease in animals does not appear to cause severe pain, except where trauma is involved. Most animals with intracranial disease can generally be managed with mild analgesics, such as butorphanol or buprenorphine. In the immediate perioperative period, more effective analgesic agents, such as methadone or pethidine, are preferred. Morphine is generally avoided because of the risk of vomiting, which is associated with significant increases in ICP. For animals with severe pain, such as head trauma patients with multiple injuries, infusions of fentanyl may be useful. Due to the short duration of action of this drug, the infusion rate can be titrated to achieve adequate analgesia and minimal respiratory depression.

Potential complications of opioid administration include bradycardia and associated hypotension as well as respiratory depression and associated hypercap-nia. Opioids are also reported to cause pupil dilation in cats and constriction in dogs, which can potentially interfere with neurological assessment. In conscious animals, these side-effects do not appear to be a problem at the low doses used clinically (Table: Advantages and disadvantages of opioid analgesic agents used for perioperative pain control in dogs and cats with neurological disease). However, these agents should still be used with care, particularly in the depressed or stuporous patient where side-effects are generally exacerbated.

Table: Advantages and disadvantages of opioid analgesic agents used for perioperative pain control in dogs and cats with neurological disease (Dose rates commonly used are also provided. aFor range of doses given, the lower doses are recommended for i.v. administration (where specified) or i.m. injection in depressed animals, and the higher doses for i.m. administration in alert animals or those in pain. bCats may have slower metabolism and may require less frequent administration. CRI = continuous-rate infusion.)

Indication Agent Advantages Disadvantages Dose regimen
Pre- and postoperative Butorphanol Good sedative Mild analgesia (kappa-agonist)

Short duration of analgesia

Antagonizes pure mu agonists

0.05-0.4 mg/kg i.v. or i.m.a
Buprenorphine Long duration (6-8 hours) Mild analgesia (partial mu agonist)

Prolonged onset (30-60 minutes)

0.006-0.01 mg/kg i.m. or s.c.aq8h
Morphine Potent analgesia (full mu agonist)

Can be used as CRI postoperatively

Nausea and vomiting

Histamine release with rapid i.v, injection

0.1-0.4 mg/kg i.v. or i.m.a q2-6hb CRI: 0.1 mg/kg/h
Methadone Potent analgesia (full mu agonist)

Moderate duration of action

Pharmacokinetics in small animals

unclear

May accumulate with repeated

dosing

0.1-0.4 mg/kg i.v. or i.m.aq2-6hb
Pethidine Potent analgesia (full mu agonist) Potent cause of histamine release

if given i.v.

Pain on i.m. injection

Short duration of action

2-5 mg/kg i.m. or s.c.q2-4hb
Fentanyl Potent analgesia (full mu agonist)

Short-acting (10-15 minutes)

Suitable for infusion

High doses cause respiratory depression CRI: 2-5 ug/kg/h Transcutaneous patches: 2-5

ng/kg

Intraoperative Fentanyl Potent analgesia (full mu agonist) Short-acting (15 minutes) Suitable for infusion Marked respiratory depression at doses used intraoperatively

Duration of action increases with duration of infusion

Bolus 1-2 ng/kg i.v. q15-20min CRI: 0.2 ng/kg/min
Alfentanil Potent analgesia (full mu agonist)

Short-acting (5 minutes)

Suitable for infusion

Marked respiratory depression at doses used intraoperatively Duration of action increases with duration of infusion 1 ug/kg/min i.v.
Remifentanil Potent analgesia (full mu agonist)

Very short-acting (1-2 minutes)

Easily titrated to effect

Duration of action is constant regardless of duration of infusion

Marked respiratory depression at doses used intraoperatively

Very rapid recovery: additional analgesia required before stopping infusion.

0.2-0.5 ug/kg/min i.v.

Supportive care

Fluid therapy

Fluid therapy is required in the neurological patient to ensure normovolaemia and normotension and to minimize alterations in electrolyte and acid-base balance. Water restriction was previously thought to decrease brain water content but it is now known that the adverse effects of this action on blood viscosity result in decreased oxygen delivery, which stimulates vasodila-tion and increases CBV and ICP ().

Fluid requirements include maintenance plus insensible losses (e.g. panting). In normal animals, maintenance requirements are 2 ml/kg/h (50 ml/kg/day). Animals receiving corticosteroids and osmotic diuretics such as mannitol are polyuric and have higher maintenance requirements; in these animals, rates of fluid administration can be adjusted according to the volume of urine produced. During surgery, dose rates of 10 ml/kg/h are generally used to accommodate for the relative hypovolaemia associated with the vaso-dilatory effect of anaesthetic agents. Blood loss should preferably be replaced by colloid or blood administration, to limit the volume of fluids administered.

The types of fluid suitable for use in patients with intracranial disease are summarized in Table Summary of crystalloid and colloid fluid characteristics and suitability for use in animals with central nervous system disease. Hypotonic solutions such as Hartmann’s can be used as long as large volumes are not required, as this could increase brain tissue water and ICP (). Isotonic crystalloid solutions are the preferred fluids where large volumes are required for rehydration or intraoperatively. Unfortunately, the only isotonic crystalloid solution available in the UK is 0.9% saline, which results in hyperchloraemic metabolic acidosis if administered for prolonged periods. In animals with normal serum electrolyte concentrations, the authors tend to use 0.9% saline intraoperatively and Hartmann’s solution for maintenance requirements perioperatively.

Adequacy of fluid therapy can be assessed by measuring CVP and urine output. Urine output is monitored by an indwelling urinary catheter attached to a sterile collection bag. Normal urine output should be 1-2 ml/kg/h. Urine output <1 ml/kg/h may indicate dehydration, particularly if accompanied by high specific gravity (SG). Using urine output to assess the hydration status of a neurological patient is complicated by administration of mannitol and corticosteroids, which results in production of large amounts of dilute urine. In these cases, daily monitoring of bodyweight can be useful.

Use of urinary catheters with closed collection systems () not only assists with monitoring fluid balance but also helps keep the animal comfortable and reduces the need for manual expression of the bladder. However, this has to be balanced against the increased risk of developing a urinary tract infection (UTI). Placement of indwelling catheters should be performed using sterile technique. Catheters are then attached to sterile closed collection systems. To prevent tension on the bladder and urethra, the collection system is bandaged to the hindlimb. Where commercial systems are not available, empty drip bags and lines are suitable alternatives. Urinary catheters should be flushed if urine output decreases to ensure that the system is not blocked with sediment. However, this should be done under sterile conditions as retrograde flushing of the catheter may increase the risk of infection. Many patients that undergo intracranial surgery have minimal neurological signs postoperatively and urinary catheter placement is not necessary.

Closed urine collection system in a dog recovering from spinal surgery. Placement of indwelling catheters should be performed using a sterile technique. Catheters are then attached to sterile closed collection systems. To prevent tension on bladder and urethra, the collection system is bandaged to the hindlimb.

Nutrition

Nutrition is extremely important and enteral feeding should be instigated in inappetent animals within 72 hours.

Oesophagostomy tubes () are preferred for enteral feeding in animals with intracranial disease, as nasogastric tubes can cause sneezing and an associated increase in ICP. In animals with brainstem lesions resulting in dysphagia and megaoesophagus, gastrostomy tubes are preferred in order to prevent regurgitation and aspiration (). Feeding should be commenced slowly. It is generally recommended that feeding be initiated at one-third maintenance for the first day, two-thirds on the second day and then full maintenance on the third day.

In animals that are interested in eating voluntarily, water and food are introduced gradually in the postoperative period (small amounts every 1-2 hours) with strict attention to the ability to swallow. Once it has been ascertained that these animals can swallow normally without regurgitation, normal feeding routines can be resumed. If there is any doubt as to whether to feed orally, a chest radiograph will help to determine the presence or absence of megaoesophagus. This seems to be more common following surgery on the brainstem. Intravenous fluid therapy is necessary until oral intake has reached recommended maintenance levels. When oral intake is reduced, supplementation with potassium chloride (KCI) is required in order to maintain normal serum potassium levels (3.5-5.5 mmol/l). Concentrations of KCI that can be added to fluids are summarized in Table: Guide for potassium chloride supplementation.

To avoid adverse cardiac effects, the rate of KCI administration should not exceed 0.5 mmol/kg/h.

Table: Guide for potassium chloride supplementation

Serum concentration (mmol/l) Amount KCI added to fluids (mmol/l) Maximum rate (ml/kg/h)
<2.0 80 6
2.1-2.5 60 8
2.6-3.0 40 12
3.1-3.5 30 15