Continuing Education Activity

Anesthesiologists have several tools for diminishing pain, awareness, movement, and the hemodynamic derangements of stress in the surgical patient. Gaseous anesthetics used most commonly today are a single gas nitrous oxide and volatile fluorinated liquids (isoflurane, desflurane, sevoflurane) administered via specific vaporizers that transform the liquids into gases that diminish and, at higher doses, eradicate patient awareness. This activity reviews the history, proposed function, clinical significance, and pertinent issues concerning of gaseous anesthetics.

Objectives:

• Review the use, advantages, and disadvantages of sevoflurane, isoflurane, desflurane, and nitrous oxide.
• Explain the risk and treatment of malignant hyperthermia.
• Outline the physiologic effects of sevoflurane, isoflurane, desflurane, and nitrous oxide.
• Summarize the types, advantages, and disadvantages of gaseous anesthetic agents and outline the role of the interprofessional team in providing pain relief using these medications.

Introduction

The history of anesthesia is a relatively recent one; if one begins with the analgesia dentist, Horace Wells, who discovered the used nitrous oxide during a dental extraction in the early 1800s. The first public showing of anesthesia occurred in October 1846, when ether was used to prevent pain during surgery at Massachusetts General Hospital. The following year, in 1847, Scottish obstetrician James Y. Simpson began using chloroform to treat childbirth pain.

In 1956, halothane came into clinical practice, but it caused fulminant hepatic necrosis, which promoted the development of new inhaled agents. Methoxyflurane came into clinical use in 1960 but was found to metabolize to nephrotoxic inorganic fluoride. Enflurane in 1972 was an improvement as it was not hepatotoxic, nor did it cause myocardial sensitivity to catecholamines like halothane. However, enflurane is also metabolized to inorganic fluoride, linked to increased seizure activity.[1]

Today, anesthesiologists have several tools for diminishing pain, awareness, movement, and the hemodynamic derangements of stress in the surgical patient. Gaseous anesthetics, used most commonly today, are a single gas nitrous oxide and volatile fluorinated liquids (isoflurane, desflurane, sevoflurane) that are administered via specific vaporizers that transform the liquids into gases that diminish and, at higher doses, eradicate patient awareness.

Function

The gaseous anesthetic with the longest history is nitrous oxide. It noncompetitively inhibits N-methyl-d-aspartate (NMDA) receptors.[2] The hypothesis is that nitrous oxide in rodents inhibits nociceptive inputs in the dorsal horn of the spinal cord by activating descending noradrenergic pathways coming from the periaqueductal gray matter in the brainstem. Nitrous oxide is unique among the inhaled anesthetics in that it exists in its gaseous form at ambient room temperatures.

There is no agreed-upon mechanism of action for gaseous anesthetics, but measurements to characterize them have been used to guide their clinical use. The potency of an anesthetic is determined by its lipid solubility and is described by the minimum alveolar concentration, or MAC, which is the concentration at the end of a breath needed to preclude movement in response to a surgical incision in fifty percent of patients. It is proposed that the cerebral cortex, amygdala, and hippocampus are target areas for gaseous anesthetics to cause amnesia, and the activation of descending pathways originating in the periaqueductal gray matter of the brainstem are the target areas for immobility.[3]

Issues of Concern

Nitrous oxide can cause expansion of gas and therefore increased pressure in closed air-filled spaces like in cases of bowel obstruction and pneumothorax. Air contains 78% nitrogen, which is significantly less soluble in blood than nitrous oxide. The nitrous oxide in the blood diffuses into the air-filled cavities faster than the air can be absorbed into the blood. Nitrous oxide also oxidizes vitamin B12, rendering it ineffective as a coenzyme, which can manifest as megaloblastic anemia, and in rare cases, neuropathy as seen in subacute combined degeneration.[4][5]

Strong bases in desiccated carbon dioxide absorbent can combine with metabolized desflurane to produce carbon monoxide. Sevoflurane also is the only fluorinated gaseous anesthetic whose metabolic products do not create carbon monoxide with desiccated carbon dioxide absorbent. Instead, degraded sevoflurane can produce compound A in the presence of desiccated carbon dioxide absorbent, leading to proximal tubular necrosis in animal studies. Clinically significant nephrotoxicity in humans has not yet been established.[6]

Malignant hyperthermia (MH) is a relatively rare but life-threatening hypermetabolic syndrome that can result from the use of gaseous anesthetics (most famously halothane) and succinylcholine. Tachycardia, rigid musculature, diaphoresis, rapid elevations in end-tidal carbon dioxide concentrations, and elevated temperature are all considered signs of malignant hyperthermia.[7] The signs can present very subtly. Dantrolene is the mainstay pharmacologic treatment of MH, administered as a rapid IV infusion (2.5 mg/kg every 5 to 10 minutes until end-tidal CO2 and muscle rigidity start to decline). Dantrolene inhibits calcium release from the muscular sarcoplasmic reticulum and blocks the coupling of muscular excitation and contraction.  Early recognition and diagnosis have led to an improvement in mortality rates from MH, but its treatment is an arduous event that requires rapid and complete cooperation of all healthcare workers in the presence of a surgical patient experiencing this disorder. 

Clinical Significance

Sevoflurane, isoflurane, and desflurane cause a decrease in systemic vascular resistance, typically seen as a decrease in mean arterial pressure (MAP). Nitrous oxide tends to have no effect on or at most causes a small increase in MAP. Gaseous anesthetics cause myocardial depression, with isoflurane being the least associated with arrhythmogenicity in patients. Sevoflurane, isoflurane, and desflurane increase respiratory rate and decrease tidal volumes. All gaseous anesthetics dilate the pulmonary vascular bed, inhibiting the mechanism of vasoconstriction of the pulmonary vascular bed when hypoxia occurs.[8]  All gaseous anesthetics cause relaxation of the skeletal muscles and also enhance the effect of neuromuscular blocking drugs. Desflurane provides the most significant enhancement of neuromuscular blockade by rocuronium.[9] 

Due to the specific impacts of gaseous anesthetics on various organ systems, their use is limited in certain types of surgical procedures. Hypoxic pulmonary vasoconstriction is a physiologic mechanism to aid in ventilation-perfusion matching, and gaseous anesthetics can clinically inhibit this mechanism.[10]  During surgeries requiring one-lung ventilation, the administration of greater than 1 MAC of gaseous anesthetics is generally avoided to prevent the attenuation of hypoxic pulmonary vasoconstriction.[11]

The clinical effects of gaseous anesthetics are determined by the alveolar partial pressure of the gaseous anesthetics, which govern the partial pressures in all other tissues of the patient's body. The effects on alveolar partial pressure are primarily the result of the amount of gaseous anesthetic delivered to the patient in the inspired gas and the amount of alveolar ventilation. As blood passes through the lungs, it takes some for the gaseous anesthetic to move into the alveoli, depending on the blood/gas solubility coefficient of that anesthetic and the patient's cardiac output; this is what is known as uptake. Increased uptake may slow the time to induction with a gaseous anesthetic. Furthermore, emergence from anesthesia is quicker with gaseous anesthetics with low blood/gas solubility.[12]

Enhancing Healthcare Team Outcomes

When gaseous anesthetics are in use, it is of paramount importance that everyone in the operating room and/or procedural site communicates well in preparation for the onset of its use and possible adverse effects. During all inductions of general anesthesia, the operating room nurse, anesthesiologist/nurse anesthetist, and surgeon should all be paying attention and be ready to assist in securing the patient's airway. Ideally, the operating room nurse is at the patient's side to assist the anesthesiologist and/or anesthetist, and in cases of an anticipated difficult airway, the surgeon should be in the room ready to establish an invasive airway.

Studies overall have been inconsistent to show other adverse effects to healthcare workers occupationally exposed to modern gaseous anesthetics. None have been shown to be teratogenic; however, nitrous oxide in large amounts can cause megaloblastic anemia due to a functional vitamin B12 deficiency.  Since the 1970s, studies have investigated the effects of waste anesthetic gases on healthcare workers exposed to them regularly. There is a suspected association with an increased relative risk for spontaneous abortions in women who are occupationally exposed to waste gaseous anesthetics. However, there are no official standards by the Occupational Safety and Health Administration (OSHA) regarding the limits of acceptable exposure.[13][14]  The safety and health of everyone in the operating room are aided when anesthesiologists, anesthetists, and anesthesia technicians ensure that scavenging systems are in place and working. Operating room nurses can confirm that operating room ventilation is active, and anesthesia providers can use low gas flow approaches to delivering general anesthesia to help minimize gaseous anesthetic waste.[15] [Level 5]

In light of this, an interprofessional team approach is the most prudent course when gaseous anesthetics are in use; this applies to both the patient and those in the operating theater performing and assisting on the procedure. The surgeon, other physicians, anesthesiologist/nurse anesthetist, and medical/surgical nursing professionals working together as a team can ensure the optimal outcome for the patient and all OR personnel involved. [Level 5]