Silverstein and Hopper Chapter 36: Anesthesia and Monitoring of the Ventilator Patient

What is the goal of induction for mechanical ventilation?

To rapidly intubate with the least likelihood of adverse effects such as cardiovascular depression

What is the mainstay of anesthesia for mechanically ventilated patients?

• Mainstay of anesthesia for mechanically ventilated patients is a continuous infusion of injectable anesthetics, typically with one or two adjunct drugs such as an opioid, benzodiazepine, and/or a-2 agonists added to reduce the amount of other anesthetic drugs needed

• Inhalant anesthesia is generally avoided, especially in patients with significant hypoxemia, as inhalants inhibit hypoxic pulmonary vasoconstriction, possibly potentiating the severity of hypoxemia

  • ICU ventilators are also not set up to allow delivery of inhalant anesthetic drugs

Anesthetic Agents and the Immune System

• Anesthetic agents, including both inhalants and those used for TIVA, have been linked to immunosuppression, with most having a direct suppressive effect on cellular and humoral immunity

  • It is generally understood that TIVA has less effect on immune function than inhalants

    • A recent study comparing the immunological effects on propofol vs isoflurane in dogs showed that propofol has less associated immunosuppression than isoflurane and may confer some immune-protective effects

MOA of Propofol

• Produces its hypnotic effect via potentiation of GABA-induced chloride current via interaction with the GABA_A receptor

Propofol for Mechanical Ventilation

• Supplied in a lipid emulsion without bacteriostatic agents

  • Use aseptic technique

  • Discard infusion set every 12 hours or if contamination occurs

• Evaluate animals on propofol infusion for lipemia regularly due to the lipid carrier

  • If develops the propofol dose should be reduced or discontinued immediately

• Typically results in a smooth induction, but myoclonus has been reported in unpremedicated dogs

• Induction with propofol titrated to effect (typically 1-4 mg/kg) followed by an infusion begun at an initial rate of 0.1 mg/kg/min IV

• Excellent choice for maintenance of anesthesia for mechanical ventilation as its rapid kinetics allow the clinician to titrate the depth of anesthesia as needed

• Propofol does not accumulate significantly in the tissues at clinical doses, it does have an increase in context-sensitive half-time as the duration of administration increases

  • Can be seen as prolonged recoveries in dogs receiving propofol and fentanyl infusions for the maintenance of surgical anesthesia for approximately 2 hours

  • In cats, recovery time appears to vary depending on dose and duration of infusion

• Administration of propofol for 24 hours for mechanical ventilation in healthy cats resulted in prolonged time to walking (18 hours) but was faster than ketamine (35 hours)

• In dogs, following 24 hours of mechanical ventilation spontaneous ventilation occurred within 1 hour of discontinuation of propofol

• Rapid recovery is important during weaning from mechanical ventilation as propofol causes dose and rate dependent hypoventilation and apnea

• Important that the patient is not overly sedated as the clinician is attempting to assess the patient's ventilatory capability as hypoventilation may occur due to the anesthetics used

• Also important that the patient doesn't become dysphoric during this period

  • Smooth recovery quality of propofol is a benefit during weaning

Risks of Propofol for Mechanical Ventilation

• Dose dependent vasodilation and myocardial depression resulting in hypotension

  • Can be particularly profound in the cardiovascularly unstable patient so sedatives and analgesics should be added to the protocol to reduce the dose of propofol required

  • Studies have demonstrated that the combination of propofol with an opioid such as morphine, fentanyl, remifentanil, or alfentanil provides improved hemodynamic stability and reduces the amount of propofol needed to maintain anesthesia

  • Another study demonstrated that mean arterial pressure could be maintained at or above 70 mmHg in dogs undergoing TIVA with propofol and fentanyl by a stepwise reduction in propofol infusion

• Propofol infusion syndrome

  •  A rare side effect of prolonged propofol infusions in humans in the ICU

  • Characerized by metabolic acidosis, arrhythmias, rhabdomyolysis, and renal railure

Alfaxalone MOA

• Synthetic neuroactive steroid anesthetic that binds to the GABA receptor in the central nervous system

  • Provides unconsciousness and muscle relaxation

Alfaxalone for Mechanical Ventilation

• Characterized as providing smooth and rapid induction of anesthesia but undesirable events at both induction and recovery have been noted occasionally, including agitation, noise hypersensitivity, excitement, head shaking, tremoring, paddling, twitching, apnea, and cyanosis

• Does not appear to accumulate following repeated bolus doses in dogs and cats

• Has been used for relatively short duration at infusion rates of 0.07-0.1 mg/kg/min

• Causes dose-dependent decreases in respiratory rate and minute volume

  • This is beneficial for the mechanically ventilated patient while trying to maintain patient-ventilator synchrony, but it may be detrimental during the weaning period

• Alfaxalone causes a dose dependent decrease in blood pressure, so dose reduction may be beneficial especially in cardiovascularly compromised patients

  • Does not appear to cause clinically significant cardiovascular depression in healthy dogs when used at an infusion rate of 0.07 mg/kg/min

    • Higher infusion rates may be associated with lower cardiac output or hypotension

• Alfaxalone's formulation contains ethanol and benzethonium chloride as preservatives so close monitoring should occur in patients, especially those with hepatic dysfunction, remaining on prolonged infusions of alfaxalone

Ketamine MOA

• Dissociative anesthetic, functioning on the NMDA, opioid, monoaminergic, and muscarininc receptors as well as voltage-gated calcium channels

• Antagonism at the NMDA receptor results in dissociation of the limbic and thalamocortical systems, resulting in a patient that does not appear asleep but does not respond to external stimuli

Ketamine for Mechanical Ventilation

• As the patient recovers from anesthesia, they are prone to abnormal behavior and emergence delirium, which may be decreased by administration of benzodiazepines, acepromazine, or dexmedetomidine

• Metabolized by the liver to inactive metabolites and renally excreted in the dog

• Potential for prolonged recoveries makes ketamine alone a less desirable anesthetic for maintenance of anesthesia for mechanical ventilation

• While ketamine as the sole anesthetic may not be desirable for maintenance of anesthesia, it does have several desirable characteristics as compared with propofol

  • Sympathomimetic effects of ketamine resulted in fewer interventions for bradycardia or hypotension in cats maintained with ketamine as opposed to propofol

  • Ketamine causes bronchodilation which may be beneficial in patients on mechanical ventilation

• Ketamine's sympathomimetic effects may lead to an increase in cerebral blood flow and intracranial pressure so it should be avoided in patients with elevated intracranial pressure requiring mechanical ventilation

Etomidate MOA

• Imidazole derivative that interacts with the GABA receptor to induce anesthesia

Etomidate for Mechanical Ventilation

• An excellent choice for induction in patients with cardiovascular disease due to its minimal effects on cardiopulmonary variable, but it is not an ideal agent for maintenance of anesthesia for prolonged periods due to its adrenocortical suppression

  • Adrenocortical suppression lasts for at least 6 hours in the dog and 5 hours in the cat following a single bolus

• Use of etomidate as an infusion has been associated with increased mortality in humans in the ICU

• Infusions of etomidate for long durations are not currently recommended so it should not be used for maintenance of patients on mechanical ventilation

Opioids for Mechanical Ventilation

• Provide sedation and analgesia

• May be administered as intermittent boluses or a CRI with no significant difference in duration of mechanical ventilation in humans receiving fentanyl infusions or propofol infusions with intermittent opioid boluses

• Ideally, select a short-acting opioid like fentanyl to allow for more rapid adjustments in infusion rates and a faster recovery

  • After prolonged infusions of fentanyl, accumulation can occur leading to a slower recovery

• Use of remifentanil, an ultra-short acting opioid, has been shown to result in rapid recoveries following discontinuation of infusion

  • May be beneficial in mechanically ventilated patients in allowing for faster extubation and decreased length of stay in the ICU

  • Significantly more expensive than fentanyl and may be associated with the development of hyperalgesia

• Opioids, such as fentanyl, is beneficial to the maintenance of anesthesia for mechanical ventilation as they have minimal impact on blood pressure or myocardial contractility

  • Their addition to propofol infusions can result in improved cardiovascular stability

• Opioids may cause dose-dependent bradycardia, which can lead to a decrease in cardiac output

  • This bradycardia is vagally mediated and can be treated with anticholinergics

• Opioids have minimal impacts on cardiovascular parameters

Side Effects of Opioids

• Decrease gastrointestinal motility which can lead to significant ileus

• Depress ventilation and are anti-tussive, which may be beneficial in preventing patient-ventilator dyssynchrony and improving tolerance of the endotracheal tube, but this can be detrimental during weaning from ventilation

• Extremely large doses of fentanyl for prolonged periods have been associated with "wooden chest" syndrome in human patients where rigidity of the chest wall occurs

• The side effects are reversible with mu antagonists such as naloxone

  • Consider that reversal of opioids will also reverse their anesthetic effects and can lead to profound distress so the smallest dose of reversal should be used in nonemergent situations

Benzodiazepines MOA

Function by enhancing the affinity of the GABA receptor for GABA, leading to hyperpolarization of postsynaptic cell membranes in the CNS, resulting in sedation, anxiolysis, muscle relaxation, and anticonvulsant effects

Benzodiazepines for Mechanical Ventilation

• May be used as an adjunct to reduce the amount of anesthetic needed for induction or maintenance of anesthesia

• Midazolam and diazepam are useful as adjuncts to anesthetic agents, when used alone they are not reliable sedative and may cause excitation in healthy animals

  • If excitation or dysphoria is observed during weaning, reversal with flumazenil may be considered

• Useful in critically ill patients as they have minimal cardiovascular and respiratory side effects

• Midazolam may be preferred as propylene glycol toxicosis can occur with prolonged administration of diazepam

  • Signs of toxicosis include lactic acidosis, hyperosmolality, hemolysis, cardiac arrhythmias, seizures, and coma

• Midazolam has been used in dogs and cats to maintain anesthesia for mechanical ventilation for 24 hours, however its use in human patients has been associated with longer periods of mechanical ventilation and increased delirium

  • No longer recommended for routine ICU sedation in human medicine

  • Adverse effects of longer term (days to weeks) infusions of midazolam in dogs and cats have not been evaluated and its commonly used as part of a TIVA protocol in ventilator patients at this time

Alpha-2 Agonists for Mechanical Ventilation

• The sedation caused may also be used to reduce the amount of induction and anesthetic maintenance agent required to maintain anesthesia

• May be administered as a bolus or infusion for maintenance of sedation and analgesia

• As an infusion given over 24 hours, it does not appear to accumulate when administered at approximately 1 ug/kg/hr

  • Beneficial in patients requiring prolonged sedation for mechanical ventilation where drug accumulation could be detrimental to rapid recovery

• Dexmedetomidine has minimal effect on ventilation with blood gas parameters remaining unchanged during infusions

• Dexmedetomidine may protect lungs from ventilator-induced lung injury

• Dexmedetomidine has been shown to be superior to midazolam for sedation of humans for mechanical ventilation

Alpha-2 Agonists MOA

• Primarily cause sedation via binding to a-2 adrenergic receptors in the locus coeruleus and rostroventral lateral medulla leading to decreased norepinephrine release

Risks of Dexmedetomidine

• Particularly in hemodynamically compromised patients because it has been shown to cause vasoconstriction with a reflex bradycardia leading to a decrease in cardiac output

  • With low-dose dexmedetomidine infusions in healthy dogs, oxygen delivery is sufficient with no increase in lactate levels observed

Acepromazine MOA

Phenothiazine that causes sedation primarily via blockade of the D2 dopamine receptors

Acepromazine for Mechanical Ventilation

• Reliable sedative in small animals

• May be beneficial in treating dysphoria during recovery from sedation for mechanical ventilation

• Minimal effects on pulmonary function with no changes in blood gas values

• Because of its long duration of action and hemodynamic effects, it is not recommended to be administered as an infusion during sedation for mechanical ventilation

  • Can cause significant hypotension via a-1 blockade leading to decreases of 20-230% in arterial blood pressure in dogs administered large doses of 0.1 mg/kg IV

  • Use low doses in hemodynamically stable patients and avoid in hypotensive patients

Neuromuscular Blocking Agents for Mechanical Ventilation

• Use of neuromuscular blocking agents (NMBAs) to facilitate ventilation is controversial

  • Some studies suggest increased morbidity when NMBAs are used for mechanical ventilation in humans

    • Has been associated with quadriplegic myopathy syndrome, critical illness polyneuropathy, and ventilator-induced diaphragmatic dysfunction

• Neuromuscular blocking drugs may be beneficial in acute respiratory distress syndrome, especially when patient-ventilator dyssynchrony cannot be corrected with adjustment of ventilation parameters

  • By causing paralysis of the diaphragm, these drugs have been shown to prevent volutrauma and barotrauma associated with patient-ventilator dyssynchrony

• NMBAs are not commonly used in veterinary medicine for mechanical ventilation but may be indicated for short periods in situations of severe acute respiratory disease syndrome patients when patient-ventilator dyssynchrony is a concern

Making an Anesthesia Plan for the Ventilator Patient

• Ensure an oxygen source is always available in case of machine malfunction

• Have anticholinergic drugs and resuscitation drugs readily available is recommended

• Suction should be available in the even of excessive secretions, regurgitation, or significant pulmonary edema or hemorrhage

• To reduce the amount of induction agent needed, can administer loading doses of planned adjunct infusions, such as fentanyl or midazolam, prior to administering the induction agent

• Anticholinergics can be used to treat clinically relevant bradycardia caused by opioids or increased vagal tone

• Maintenance anesthesia plan is based on the patient's clinical status, and estimation of the likely length of anesthesia required, and potentially the financial situation

• Critically ill animas with cardiovascular compromise will need very low doses (if any at all) of an anesthetic drug and can be maintained primarily on adjunct agents

• A cardiovascularly stable and relatively healthy patient will need an anesthetic drug in combination with one or more commonly two adjunct agents

Withdrawal of Anesthesia for Ventilator Weaning

• The goal for weaning the patient from the ventilator is that they smoothly and rapidly recover from anesthesia to allow for return to successful spontaneous ventilation

• Important to withdraw NMBAs first as residual blockade can greatly impact ventilation as well as pharyngeal and laryngeal function

• When possible, ketamine and midazolam should also be discontinued as early as possible as they can accumulate and lead to dysphoria in the recovery period

  • If dysphoria from midazolam is suspected, it can be reversed with flumazenil

• Depending on the depth of sedation or anesthesia needed to tolerate intubation, the recovery process may be prolonged

• Typically patients with tracheostomies require less sedation than those intubated orally and may recover more quickly

  • These patients can also be placed back on the ventilator relatively easily without the need for re-induction of anesthesia

• As the patient's propofol or alfaxalone is discontinued, they may become distressed or dysphoric

  • During this period a low dose of acepromazine (0.002-0.005 mg/kg) may be helpful to reduce dysphoria

  • If the patient had been maintained on a dexmedetomidine infusion, this can be continued at a lower rate into the recovery period to prevent dysphoria

• The infusion of opioids should be decreased or discontinued dependent on the patient's anticipated analgesic requirements

  • If the patient is not painful and the opioid is thought to be contributing to prolonged sedation, hypoventilation, or dysphoria, it can be reversed with naloxone

What is the most common heart-lung interaction noted with the onset of PPV

Acute reduction in venous return

• May be magnified in veterinary patients requiring induction agents that inherently carry some cardiovascular depressive effects

• Reduction in venous return may also be more pronounced in hypovolemic patients or those with inappropriate vasodilation secondary to sepsis

What often causes decreased cardiac output secondary to PPV?

Often the result of high airway pressures (increases in mean airway pressure have a more negative effect on cardiac output than changes in peak inspired pressure), increased lung compliance, and decreased circulating volume

Monitoring Blood Pressure in Ventilated Patients

• Continuous blood pressure monitoring via arterial catheterization is ideal and also allows for more regular blood sampling

• Frequent monitoring with noninvasive blood pressure devices (Doppler or oscillometric) is often adequate

• Normal blood pressure does not indicate hemodynamic stability if compensatory mechanisms remain intact

• Changes in blood pressure with alterations in ventilator setting may indicate a decrease in cardiac output

  • It is also possible that there may be a significant drop in cardiac output with adjustments in ventilator settings with no accompanying change in blood pressure

• Blood pressure may be a specific, but insensitive, indicator of changes to cardiac output

What can cause bradyarrhythmias in the ventilated patient?

May be the result of high vagal tone secondary to respiratory disease, manipulation of the airway or endotracheal tube, gastric distension, traumatic brain injury, or electrolyte abnormalities

What can cause ventricular and supraventricular ectopy in a ventilated patient?

• Ventricular and supraventricular ectopy are also common and may precipitate with given change in volume, sympathetic and parasympathetic tone or as a result of myocardial ischemia

Electrocardiogram for Monitoring the Ventilated Patient

• Continuous electrocardiogram should be placed on every patient to evaluate for rhythm disturbances

• Dysrhythmias are a common complication of mechanical ventilation and may be compounded by the use of sedation/anesthesia or the underlying disease process and often indicate and/or lead to cardiovascular instability

• Cardiovascular instability is a common cause of weaning failure and standard perfusion parameters are often insensitive markers of cardiovascular dysfunction

  • Changes in arterial blood pressure and/or heart rate may be early indicators of impending weaning failure and myocardial ischemia that may be precipitated by the patient's increased work of breathing

Blood Gases for Monitoring the Ventilated Patient

• Arterial blood gas assessment allows for evaluation of oxygenation, ventilation, and acid-base status

• Venous blood gas can allow for monitoring of PCO2 but cannot be used to assess oxygenation

Pulse Oximetry for Monitoring the Ventilated Patient

• Offers continuous, noninvasive evaluation of SaO2, which can aid in identification of arterial desaturation and allow rapid adjustments in ventilator settings, including FiO2, PEEP, tidal volumes and airway pressures

• Provides little indication of the patient's acid-base or ventilatory status so changes in pH and PaCO2 may occur with little to no change in the SpO2

• Relatively insensitive measure of detecting hypoxemia when the patient has a high baseline PaO2 so it is possible that a relatively significant drop in PaO2 may go undetected if the patient is hyperoxic at the outset

• Pulse oximeters with an arterial waveform may also recognize variations in stroke volume associated with gas trapping or auto-PEEP and the respiratory variation in the waveform amplitude may be a useful indicator of fluid responsiveness

When are pulse oximeters accurate?

• Pulse oximeters are accurate when the pulse quality is good and the saturation is >80%

  • With progressive desaturation, movement artifact or dyshemoglobinemias, as well as changes in perfusion, including low cardiac output, vasoconstriction, and/or hypothermia, pulse oximetry becomes less reliable

Capnography for Monitoring the Ventilated Patient

• Sampling of CO2 may be achieved by using either mainstream or side stream analyzers that are attached to the endotracheal tube

  • May underestimate the degree of hypoventilation in patient with higher PaCO2

• Partial obstruction of the endotracheal tube may lead to gradual increases in exhaled CO2 despite maintaining a normal ETCO2

• Rebreathing CO2 may increase both the inspired and expired CO2

• A curare cleft may be visible on the capnogram in a patient taking spontaneous breaths during mechanical ventilation and may indicate inadequate sedation or patient-ventilator dyssynchrony

What is the difference between ETCO2 and PaCO2 in healthy patients?

1-5 mmHg

P(a-ET)CO2 Gradient

• The normal P(a-ET)CO2 gradient is the result of dilution of alveolar gas by gas in the physiologic dead space

• In mechanically ventilated patients with abnormal lung function, there is much more variability in the P(a-ET)CO2 gradient, making the prediction of PaCO2 from ETCO2 less reliable

  • An increase in P(a-ET) CO2 may indicate an increase in alveolar dead space secondary to severe pulmonary parenchymal disease, decreased cardiac output, or obstruction to blood flow such as occurs with pulmonary embolism

• The P(a-ET)CO2 gradient may be used to detect optimal levels of PEEP and should be the smallest when there is maximal recruitment of lung units participating in gas exchange without overdistension

What can cause overall changes in ETCO2?

• CO2 production

• CO2 delivery to the lungs or alveolar ventilation

What can cause sudden increases or decreases in ETCO2?

• Sudden increases or decreases in ETCO2 may be associated with equipment malfunction, changes in cardiac output and obstruction of pulmonary blood flow was may occur with pulmonary thromboembolism or air embolism

What does absence of ETCO2 indicate?

Esophageal intubation or cardiac arrest

Monitoring Temperature in the Ventilated Patient

• Hypothermia is a common consequence of anesthesia

• Hyperthermia will stimulate increased respiratory rate and can lead to patient-ventilator dyssynchrony