NITROUS OXIDE

NITROUS OXIDE

Nitrous oxide was first synthesized in the late 1700s as a colorless and almost odorless gas, and its anesthetic and pain-relieving properties were appreciated almost immediately. For quite a while it remained out of the mainstream of medicine, being used mostly for recreation and entertain‑ment at carnivals. The first medical usage of this gas came in the mid-1800s when dentists found it to be an excellent way to suppress pain.

One cannot easily achieve deep surgical anesthesia with nitrous oxide alone, unless it is applied in an environment where the atmospheric pres­sure is raised. Now it is used medically only to augment other anesthet­ics and sedatives, or for minor procedures that do not require the loss of consciousness. When nitrous oxide is inhaled in sufficient quantity, there is a euphoric feeling that comes along with the pain relief The term laughing gas arises from the giddy state that it produces. By comparison to any of the other drugs that people inhale for recreation, nitrous oxide is safer, because it has little effect on critical body functions including respiration; brain blood flow; and liver, kidney, and gastrointestinal tract processes.

The pharmacological mechanisms of nitrous oxide have not been com­pletely determined. Certainly it acts like a general anesthetic and under high pressure can cause loss of consciousness, so, as we suspect with other anesthetics, it may increase GABA inhibition of nerve cells. Part of its effect may also be through the brain's built-in opiate system—the same receptors that morphine and heroin activate. One of the best bits of data that support this is that the specific opiate antagonist naloxone blocks the pain-relieving properties of this gas in animal experiments. In fact, nitrous oxide has been used to treat opiate and alcohol withdrawal symptoms.

The latest research studies suggest that nitrous oxide may also act on a neuronal receptor for the neurotransmitter glutamate, the N-methyl-D­aspartate (NMDA) receptor. This is the same site at which ethanol and ketamine act to produce their dissociative effects—that feeling of being out of your body. NITROUS OXIDE TOXICITY AND TOLERANCE

As we described, in clinical settings nitrous oxide is rather free of toxic effects. However, for recreational users, there are four dangers: not getting enough oxygen, getting hurt if the gas-delivery device works improperly, experiencing a vitamin B12-related problem that might occur with repeated use, and suffering possible brain toxicity if nitrous oxide is used in combination with other drugs that are NM DA antagonists.

First, remember that nitrous oxide is an anesthetic gas that can cause unconsciousness, or at least make you so disoriented that you lose good judgment. Major problems occur when the user arranges some sort of mask or bag to deliver pure gas and then becomes unconscious and breathes only nitrous oxide: the person is asphyxiated by lack of oxygen.

Second, there is the physical damage to tissues exposed to any gas that is expanding. Anyone who has ever held her hand in front of an air or gas jet knows that expanding gas is cooling. That's the principle underlying air-conditioning units. Some users try to inhale the gas right out of the tank with no regulation of the flow rate, actually injuring their mouths, tracheas, and lungs from the cooling gas. Also, there is the direct physical

risk of overexpanding (blowing up) the lungs as the gas flows at a high vol­ume and pressure.

Third, there is an odd complication of prolonged nitrous oxide use that is similar to a vitamin B12 deficiency. A B12-dependent enzyme is inacti­vated by nitrous oxide, and that leads to the destruction of nerve fibers (a neuropathy) and thus neurological problems. These can include weak­ness, tingling sensations, or loss of feeling. There are several case reports in the medical literature of nitrous oxide causing severe nerve damage.

Some dentists who regularly administer this gas have been found to expe­rience this type of neuropathy.

Fourth, animal studies now suggest that NIVIDA-receptor blockers like nitrous oxide can be neurotoxic in certain brain areas. The combination of ketamine and nitrous oxide suggests that using these drugs together might be particularly problematic. In animals, they are synergistic, pro­ducing much more damage together than would be expected from the simple combination of the two drugs. This should serve as a strong cau‑

tion to recreational users of nitrous oxide not to combine that use with any other NMDA antagonist like ketamine or ethanol.

Tolerance to nitrous oxide can develop, and the euphoric properties

diminish with repeated usage. However, in the recreational setting, where it is used only occasionally, tolerance is unlikely.

NITROUS OXIDE AND OTHER GAS ANESTHETICS

NITROUS OXIDE AND OTHER GAS ANESTHETICS

WHAT THEY ARE AND HOW THEY WORK

One of the most important drug experiences anyone can have is that of proper anesthesia in the operating room. Most surgery could not be car­ried out without proper anesthesia, because it serves three important functions: pain relief, muscular relaxation, and loss of consciousness. All of the gas anesthetics produce the loss of consciousness, and some of them produce the muscle relaxation and pain relief The reason for pain relief is obvious: No one would want to be cut and probed without pain suppression. Because most general anesthetics produce only loss of con­sciousness and not pain relief, a pain suppressor is added by an anesthesi­ologist. Muscular relaxation is required so that involuntary muscle contractions will not get in the way of the surgeon's work. Finally, the loss of consciousness provides the patient relief from the anxiety and bore­dom of the operating room and perhaps some very welcome amnesia for the whole experience. It is probably this characteristic of gas anesthetics that leads to their abuse.

Surgery wasn't always so easy. Until 1847 it was carried out without the help of anesthetic agents. Before then, there might have been a little help from alcohol or opium, but mostly the patient was held down by an array of strong men while the surgeon worked in spite of the patient's screams. But in 1847 things changed at the Massachusetts General Hospital when ether was first used, Ether had been synthesized recently, and dentists had begun to notice that it had anesthetic properties. A dentist named Mor­ton claimed that he could produce surgical anesthesia with this miracle compound and that he would demonstrate it at Mass General. With the observation gallery full and the men arrayed to hold down the patient as usual, the dentist appeared with the anesthesia machine he had invented to administer the ether. For the first time a patient underwent major sur­gery while asleep but with his heart and respiration safely intact. Within a month the word had spread and ether became a powerful part of medi­cine and surgery.

Ether was a great general anesthetic because it fulfilled the requirements for anesthesia, but it was flammable and could cause operating room fires. Modern nonflammable anesthetic agents, like halothane, are both effec­tive and potent, and anesthesia is achieved by breathing air containing just a small percentage of these gases. This makes them great for the operating room and bad for drug abusers, because it is so easy to overdose with them. As higher levels of anesthesia are achieved, three significant systems are impaired: respiration, blood pressure, and heart contractions.

Breathing is produced by the firing of a group of nerve cells deep in the brain. They are a little resistant to anesthetics, but at high levels their activity is suppressed, and respiration is depressed. Also, the smooth muscle cells that keep blood vessels at a set diameter relax, and this causes a drop in blood pressure. Finally, anesthetics can have a direct effect on the ability of the heart to contract, so it becomes weaker and prone to dis­ruptions of its rhythm. Halothane is particularly tricky because the dif­ference between the concentration that is effective and the one that causes problems is small.

Lots of chemicals and gases can be anesthetic agents, ranging from inert gases like xenon to the most modern compounds. Scientists still do not know exactly how anesthetics work. We know that they suppress the firing of nerve cells, and some can relax various muscles. At this point the best evidence is that, in part, they suppress consciousness by increasing the action of the neurotransmitter GAF3A (see the "Brain Basics" chapter for an explanation of GABA), which inhibits excitable activity in neural

networks.

When an anesthetic gas is inhaled, the sequence of responses is fairly uniform for many of the agents. There can be a brief period of excitation or stimulation, like after the first drink of alcohol. This is followed by pain relief, dizziness, weakness, and general depression of functions. At higher levels, reflexes such as eye blinking, swallowing, and vomiting can be lost. Finally, heart function and respiration are lost and the person dies. Some agents (such as enflurane) have more excitatory effects at overdose, and at high levels these effects can cause epileptic seizures. Other agents produce little in the way of stimulation and only depress the nervous system.

The window of concentration between anesthesia and death is very nar­row for these drugs. In medical settings the gases are carefully mixed with oxygen and survival body functions are monitored continuously. The anesthesiologist is fully capable of maintaining breathing for the patient or administering cardiac stimulants if necessary. Even with this level of care, problems can occur. Without careful surveillance, a person is at enormous risk of either dying or sustaining permanent brain damage.