Abstract
The above famous critique of intravenous anesthesia occurred following the bombing of Pearl Harbor, where anesthesia folklore tells us more Americans died from the use of thiopentone than from the Japanese attack. However, in the same journal that published Halford’s statement there appeared a case study of the use of thiopentone in a shocked patient with a gunshot wound to her chest and upper abdomen.
As Admiral Gordon-Taylor of the British Navy has so aptly said, “Spinal anaesthesia is the ideal form of euthanasia in war surgery” – then let it be said that intravenous anesthesia is also an ideal method of euthanasia”
The above famous critique of intravenous anesthesia occurred following the bombing of Pearl Harbor, where anesthesia folklore tells us more Americans died from the use of thiopental than from the Japanese attack. However, in the same journal that published Halford’s statement there appeared a case study of the use of thiopental in a shocked patient with a gunshot wound to her chest and upper abdomen.2 In this case the anesthetist administered a more modest bolus of thiopental (25 mg compared to the 500 mg boluses used at Pearl Harbor), supplemented anesthesia with nitrous oxide, secured the airway with endotracheal intubation, and allowed the patient to breathe spontaneously.
The austere environment of disaster medicine provides the anesthetist with a number of challenges. including:
1. Logistics of supply and re-supply of drugs and equipment
2. Prolonged evacuation times
3. Reduced specialist support
4. Limited and unreliable power and medical gas supply
5. Exposure to extremes of temperature and dust.
While high fidelity and complex anesthetic machines have allowed the First-World anesthetist to handle sicker and more complex patients, they are unlikely to function in the above environment. In this setting total intravenous anesthesia can offer the anesthetist many advantages over volatile anesthesia. Volatile anesthetics are affected by temperature and can be a logistical burden as large volumes are required. Volatile anesthetics are also classed as dangerous cargos by airlines and are unable to be transported in passenger baggage.
Disadvantages of Volatile Anesthesia
Logistics of supply
Volatiles are “dangerous cargo”
Requirement for scavenging
Storage issues (temp requirement of large volumes)
Varied performance at extremes of temperature
Agents are very costly due to large flows
Many anesthetists are unfamiliar with draw-over vaporizers.
Total intravenous anesthesia (TIVA) is a technique for providing general anesthesia using only intravenous agents. In the First World it is normally performed by syringe drivers controlled by complex pharmacodynamic formula,3 but in a resource-poor situation it can be performed using a simple ml/h syringe driver, a gravity-fed intravenous infusion set, or, in its simplest form, by intermittent boluses.
Propofol
Due to its favorable pharmacokinetics the most common agent used for TIVA in hospital-based anesthesia is propofol.4 The simplest regimen delivers a bolus followed by infusion at a reducing rate as fat stores become saturated. This is known as the Bristol method, which produces a plasma propofol concentration of 3 to 3.5 μg/ml by delivery of a 1 mg/kg bolus followed by an infusion that decreases from 10 to 8 to 6 mg/kg/h every 10 minutes.5
Following an intravenous injection the drug is lost from the plasma by redistribution into the tissues, metabolism, and pulmonary and renal clearance. A graph of plasma concentration vs time reveals that the plasma concentration falls in a triexponential manner, with the pharmacokinetics best being described by a three compartment model.6 In order to maintain a steady-state plasma concentration the lost drug needs to be replaced by a stepwise decreasing infusion. Depth of anesthesia can be increased by a bolus followed by an increase in the infusion rate. Anesthesia depth is decreased by pausing the infusion for a short period before re-starting it at a lower rate.
Whilst propofol has many advantages as an agent for TIVA, in the situation of disaster and austere medicine it has some drawbacks. Its pharmacokinetics and dynamics are adversely affected by hemorrhagic shock7 such that compartmental clearances are reduced and volume of distribution is increased, leading to an increased plasma concentration of propofol. This effect is compounded by an increase in patient sensitivity to the drug leading to a two and a half times reduction in the plasma concentration required to achieve anesthesia. Whilst the effect of hemorrhagic shock on propofol pharmacokinetics is reversed by volume resuscitation, pharmacodynamic effects of hemorrhage are unchanged.8 Propofol is also affected by storage temperature, and has adverse effects on respiration, requiring a high level of monitoring and vigilance in order to ensure an adequate safety profile.
Ketamine
Ketamine is the most widely used intravenous anesthetic in disaster medicine. It has a number of advantages for its use in this situation, including a very wide safety profile.9 Ketamine is a dissociative anesthetic. Its mechanism of action is through competitive antagonism of the excitatory neurotransmitter glutamate at the N-methyl-D-aspartate receptor Ca2+ channel, thus disconnecting the thalamus from the neocortex.10 It is prepared as a racemic mixture in an acidic solution. It is commonly presented as the ketamine hydrochloride salt in 200 mg per 2 ml and 500 mg per 10 ml ampoules. It is soluble in water and is able to be mixed with other acidic drugs such as midazolam, propofol, fentanyl, morphine, and vecuronium.
Advantages of Ketamine
Wide safety profile
Available in high concentrations allowing easy carriage
Provides good analgesia, allowing it to be used as a sole anesthetic agent
Safer in hemorrhagic shock
Respiration and airway reflexes relatively maintained
Can be given orally, IM or IV
Doesn’t trigger MH.
Ketamine Pharmacokinetics
Ketamine is metabolized in the liver by hydroxylation and demethylation to norketamine which is excreted in the urine. When given intravenously it has an onset of action of 30 seconds, a distribution half life of 10 minutes, and an elimination half life of 2 to 3 hours. Unlike propofol, its pharmacokinetics are best described by a two-compartment model.11 Ketamine is also well absorbed when given intramuscularly, having a bioavailability of 90 to 95%. When given via this route a 6 to 8 mg/kg dose has an onset of 3 to 5 minutes and duration of up to 25 minutes.
Ketamine Pharmacodynamics
Ketamine’s pharmacodynamics have been well described in the literature.12 The dissociative anesthetic state it produces is quite different to other anesthetic agents. There is no loss of corneal reflex such as occurs with other induction agents and it often produces a slow nystagmus, with dilation of the pupils. Its use is often associated with non-purposeful movements, which can be of concern to anesthetists and surgeons not familiar with its use.
Cardiovascular Effects
Ketamine produces favorable hemodynamics as a result of inhibition of re-uptake of norepinephrine.13 This often results in an increase in heart rate, systemic vascular resistance, and blood pressure. These affects make ketamine anesthesia a particularly good choice in hypovolemic and unstable patients, but can be blunted by the co-administration of midazolam or opiates.14 Of note, however, is that ketamine has direct cardiac inhibitory affects which are unmasked when the sympathetic nervous system is exhausted, resulting in a fall in blood pressure.15
Respiratory Effects
The effects of ketamine on the respiratory center are also of advantage to the anesthetist involved in disaster surgery. Ketamine causes bronchodilation which is of benefit to patients with exposure to toxic gases, as might occur in a disaster situation. Ketamine also maintains respiratory drive much more than other anesthetic agents, improving its safety profile and lessening the risk of airway loss and the requirement to ventilate a patient under anesthetic. Ventilation perfusion mismatch is less with ketamine compared to other anesthetic agents.16 These properties can result in a lower inspired oxygen concentration requirement, in some cases being able to provide anesthesia without any added oxygen.17 This relieves a large burden to the anesthetist operating in an austere environment with limited gas supplies.
Salivation is increased with ketamine, which could possibly cause laryngospasm or upper airway obstruction. Secretions can be reduced by pre-medication with either atropine or glycopyrolate; however, care is needed in tropical environments as the concurrent decrease in sweating caused by these agents may lead to hyperthermia. Although swallowing and gag reflexes are maintained with this anesthetic more than with other IV agents, aspiration is still possible and so care is needed when the patient is unfasted, which is likely in a disaster situation.
Many anesthetists in the past have avoided ketamine in patients where pulmonary hypertension may be present as it had been reported to increase pulmonary vascular resistance; however, this action does not occur when hypercapnia is controlled by mechanical ventilation.18,19
Central Nervous System Effects
In the past the use of ketamine in head injury has been controversial as there were case reports of increase intracranial pressure during ketamine anesthesia.20,21 Review of these case reports reveals that end-tidal CO2 was not controlled. A recent review article has challenged previous doctrine and suggests that ketamine is safe in the setting of head injury, if attention is paid to avoidance of secondary injury caused by hypotension, hypoxia, and hypercapnia.22 In view of its favorable cardiac effects, ketamine may be a better choice than propofol in the hemodynamically compromised trauma patient with a co-existing head injury.
One of the most disturbing side effects of ketamine is that of emergence phenomenon. This can take the form of alterations in mood, vivid dreaming, and visual hallucinations to frank delirium. The incidence is of the order of 3 to 30%, increases with age and is more common in females. Pre-medication with benzodiazepams such as midazolam (0.05–0.1 mg/kg) or diazepam (0.1–0.2 mg/kg)23 reduce the incidence of this, as does co-administration with propofol. In the pediatric population the incidence and severity of delirium is significantly less; midazolam has not proved to decrease the incidence in children and is avoided, since its use may increase unwanted side effects such as respiratory depression.24 In a disaster situation, injured patients requiring surgery risk developing PTSD. It is reasonable to question whether ketamine anesthesia is implicated in the etiology of PTSD. However, a study involving US military personnel compared the incidence of PTSD between a group receiving ketamine infusion and a control group receiving only morphine analgesia for burns surgery. The incidence of PTSD was lower in the ketamine group.25 Research has recently been commenced investigating ketamine as a treatment for PTSD.26
Other Effects
Ketamine causes an increase in muscle tone. This may cause difficulties in reduction of joint dislocation or fractures, and in laparotomy requiring abdominal muscle relaxation for surgical access. The use of a muscle relaxant such as vecuronium negates this issue, at the cost of a more complex anesthetic, necessitating endotracheal intubation, ventilation, and the increased monitoring that is required with muscle paralysis.
Ketamine also increases smooth muscle tone. A study on pregnant females by Oats et al. found that uterine tone during the first and second trimesters of pregnancy was increased with ketamine to the same extent as ergotamine, but there was no increase in uterine tone in the third trimester.27 There are no studies on teratogenicity of ketamine and the FDA has listed ketamine as a category B medication. Except in cases of eclampsia and pre-eclampsia, the World Health Organization recommend ketamine as a suitable anesthetic for cesarean sections.28
Related posts:
Chapter 5 – Inhaled Anesthetics and Draw-Over Devices in Disaster Response
Chapter 6 – Airway Management
Chapter 15 – Chemical and Radiologic Exposures in Trauma and Disasters
Chapter 16 – Pain in Disasters
Chapter 12 – High-Altitude Physiology and Anesthesia
Chapter 21 – Operation Tomodachi: Anesthetic Implications
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