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Acute Circulatory Emergencies
ACUTE CIRCULATORY EMERGENCIES EDWIN R. RUZICKA PROBLEMS arising in the circulatory system provide the anesthesiologist with many emergencies to test his diagnostic ability and his skill in handling unexpected complications. It is not possible to foresee all emergencies but it is sensible to consider which ones may occur and to prepare to treat them. This preparation includes the laying aside in a known place of equipment and drugs which may be needed. Most important~ however, is the fact that these emergencies have been thought of and a method of treatment prepared. This sort of preparation will save lives as well as many purposeless movements of indecision. When it becomes necessary to operate on a patient who has been bleeding or is still bleeding it is, of course, necessary to have large quantities of blood on hand ready for transfusion. This blood should be typed and cross matched before the anesthesia is begun. It is important to realize that when gastric bleeding occurs, a Levin tube or even an Ewald tube may not necessarily evacuate all blood clots from the stomach. When general anesthesia is used the endotracheal tube with inflatable balloon cuff should be inserted with the aid of topical anesthesia before the agent producing unconsciousness is administered. After spinal anesthesia has been induced the endotracheal tube with inflatable cuff should be inserted before unconsciousness is produced when it is the plan to use spinal anesthesia plus a sleep producing agent. The purpose of these precautions is to prevent the aspiration into the trachea of foreign material should the patient vomit or regurgitate stomach contents because of the relaxation produced by the anesthesia itself. During anesthesia and surgery, acute hemorrhage is recognized by everyone and little time is lost in replacing the extravasated blood. Slower, less spectacular but consistent bleeding may be overlooked until the patient suddenly develops hypotension, rapid pulse, shallow rapid breathing, pallor and cold wet skin. A glance at the sponge rack will show many blood-soaked sponges and inspection of the operative area will reveal markedly blood-stained towels and drapes. The loss of blood is apparent but the patient must go through a critical period which could have been avoided.
CHOICE OF ANESTHESIA
The choice of anesthesia for the patient who is hemorrhaging or in shock is general anesthesia or a combination of local and general anesthesia. When better relaxation of abdominal musculature is required, the need is met by using one of the muscle relaxing drugs, such as curare. Spinal anesthesia is not the anesthetic method of choice. Spinal anesthesia produces peripheral arteriolar and capillary dilatation because of the temporary paralysis of the sympathetic nerves. A great deal of blood 713
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consequently stagnates in these areas. The result is a reduced venous return to the heart, a diminished cardiac output and a fall in blood pressure. When this is superjmposed on a circulatory system already taxed to the utmost in an attempt to retain normal physiologic activity, the result may be disastrous. EMERGENCIES OCCURRING DURING INDUCTION OF ANESTHESIA
The accidental intravenous administration of a local anesthetic agent may produce alarming symptoms during the induction of local anesthesia. The patient may become apprehensive and nervous or become very quiet and lapse into unconsciousness. Other symptoms are pallor and increased perspiration. The patient may also show respiratory irregularities such as sighing, dyspnea and shallow breathing. The pulse is usually slow and poor in quality. Twitching may begin around the eyes and nose and develop into generalized convulsions. Treatment must begin immediately. No further attempt to administer the anesthetic should be made. Oxygen should be administered immediately. Intravenous barbiturates such as nembutal or pentothal should be given to minimize the symptoms or to stop convulsions when they occur. Vasopressor drugs should also be used in the treatment of hypotension if it develops. Another circulatory emergency occurring during the early stages of anesthesia is the accidental intra-arterial injection of barbiturate drugs. As soon as injection begins, the patient complains of intense searing pain in the arm and fingers. The skin of the hand and forearm usually becomes blanched and the radial pulse is not palpable. These are indications of a severe, widespread vasospasm of the blood vessels in the arm. The in~ jection of drug should be immediately discontinued. A stellate ganglion block on the same side should be done as quickly as possible. This will usually relieve the vasospasm and pain. It may be necessary to repeat the block two or three times on successive days. This treatment has a tendency to relieve vasospasm and may prevent thrombosis of the artery. EMERGENCIES ARISING AFTER ANESTHESIA HAS BEEN ESTABLISHED
The peripheral arteriolar and capillary dilatation which spinal anesthesia produces by temporarily paralyzing the sympathetic nerves may cuse hypotension. This may be dangerous in some patients and should always be considered unphysiologic. A systolic pressure of 80 mm. of mercury is usually considered the critical level for any patient. The individual must be considered, however, and anyone who has had a sustained hypertension for a long period of time should probably not be allowed to develop a systolic pressure of less than half the usual pressure. When it is thought desirable to be able to control the blood pressure as much as possible it is good practice to have constant intravenous fluids running. If it becomes necessary to raise the blood pressure, neosynephrine, 1 per cent, may be added to the solution. A satisfactory method to follow is to mix 1 cc. of neosynephrine with 500 cc. of fluid or 2 cc. of
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neosynephrine with 1 liter of fluid. The blood pressure level may be regulated by manipulating the speed of flow of the prepared solution. This method of controlling the blood pressure may be carried over into the postoperative period with little or no trouble. N eosynephrine should never be added to a blood transfusion since the patient may need the blood badly but not need the stimulating effect of the neosynephrine. The neosynephrine solution may be added to the tubing through which the transfusion or other fluid is running by piercing the tubing with the needle of the neosynephrine set and taping the needle in place. The solutions may then be controlled independently of each other. The intravenous use of drugs to raise the blood pressure may not be necessary. Neosynephrine, 1 per cent, 2 minims, may be given subcutaneously or intramuscularly. Neosynephrine used in this manner has a tendency to raise the blood pressure rather markedly but the rise is not sustained. Melville and 'ater Raginsky suggested the intramuscular use of a mixture of 25 mg. of ephedrine and 5 units of pitressin. The blood pressure rise which results is not rapid but is sustained over a longer period of time than the blood pressure rise from neosynephrine. While vasopressor drugs are valuable for the support of blood pressure when the hypotension is due to the temporary paralysis of the sympathetic nerves by spinal anesthesia, they must never be used as substitutes for fluids or blood in surgical shock. Respiratory depression from any cause will initiate a chain of events which may result, among other things, in a marked hypotension. Too heavy premedication or overdosage of the anesthetic agent will cause inefficient respiratory movements. The inspiratory thoracic movement which brings blood into the great veins of the chest is impaired and the flow of blood into the right side of the heart is reduced. The result is inefficient cardiac action with a lessened outflow of blood and a fall in blood pressure. Decreased respiratory movements cause anoxemia and anoxic anoxia. The cerebral and medullary centers are then depressed because of oxygen lack. A vicious circle of deepening respiratory depression is thus instituted. The blood pressure fall which results from the changes produced by respiratory depression may be further aided by depression of the carotid sinus mechanism and the loss of its compensatory action. CAROTID SINUS REFLEX
It is important to bear in mind the possibility of a hypersensitive carotid sinus reflex whenever surgery of the neck is undertaken. The carotid sinus is located at the bifurcation of the common carotid artery on each side of the neck. Most anesthetic agents depress the carotid sinus but sometimes the application of pressure in the neck may start a severe circulatory reaction. This is seen, for example, during the course of a thyroidectomy when manipulation and pressure from retractors in the area of the carotid sinus may produce disappearance of the pulse and blood pressure or marked bradycardia and hypotension. Respiratory depression may occur at the same time but does not invariably do so.
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When this reaction occurs, packs and retractors should be removed and 1 per cent solution of procaine injected in the area of the bifurcation of the common carotid artery. The systemic blood pressure, pulse and respiration will return to normal in a few minutes and operation may be continued. This reaction can occur when the cervical abscess in Ludwig'S angina is incised. Safeguards against this reaction include the maintenance of a clear airway, avoidance of pressure on the neck and the use of atropine preoperatively to depress the parasympathetic nerves involved. CARDIAC ARREST
Sudden cardiac arrest may occur without warning during anesthesia. The surgeon is not usually the first to establish the diagnosis of cardiac arrest unless the operation he is doing is such that an artery is under direct vision and he notes cessation of pulsation in it. The anesthesiologist is most frequently the first to become awarl' of this complication. A constantly alert watch must be maintained for this condition by both the anesthesiologist and surgeon since cardiac arrest may occur at any time during the induction and maintenance of the anesthesia and at any stage of the operative procedure. The type of operation performed is of no assistance in anticipating or preventing sudden cardiac arrest since it may occur during any type of operative procedure. It may also occur with any anesthetic agent or combination of agents, including spinal anesthesia when used as the sole anesthetic method. The anesthesiologist must notify the surgeon as soon as the pulse and blood pressure disappear. If he even suspects that there has been a cardiac arrest, the surgeon must be asked to check arterial pulsations. False alarms will inevitably occur but must be tolerated. The short time during which treatment must be applied to be effective means that the anesthesiologist and surgeon cannot waste time in useless checking, but must be ready for instant decision and rapid institution, of emergency measures. A plan of action which we have presented before and see no reason as yet to change is as follows: (1) artificial respiration is started with 100 per cent oxygen; (2) cardiac massage is begun immediately by the surgeon-this is the all important step; (3) drug therapy is given consisting of the use of procaine and epinephrine, and (4) general methods of treatment are followed including the administration of intravenous fluids and the institution of 5 to 10 degree Trendelenburg position. Artificial respiration with 100 per cent oxygen presupposes that the airway is unobstructed. This may necessitate the insertion of an endotracheal tube. Artificial respiration with 100 per cent oxygen maintains a high concentration of oxygen in the alveoli and also may have some mechanical effect on maintenance of circulation. The return of cardiac activity does not always signal the immediate return of respiratory activity. It may be necessary to continue artificial respiration from a few minutes to several hours after the reappearance of cardiac activity. Artificial respiration is useless unless the circulation is maintained. Cardiac maSsage is the mainstay of treatment and must be started im-
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mediately if the outcome is to be favorable. The approach depends on the operative procedure but resolves itself into three routes: (1) transperitoneal subdiaphragmatic; (2) transperitoneal transdiaphragmatic, and (3) transthoracic. The rate of cardiac massage has been quoted at various figures. Many rates have been suggested but Gunn seems to have offered a really plausible figure with an explanation for his contention. He maintained that massage of the heart is not a question for indifference but that attention to detail is important. He even suggested practice for this maneuver. Gunn stated that compression should be gradual and relaxation abrupt, with rate of compression, at most, only half the normal rate. The massage must be interrupted at regular short intervals for a few seconds in order to allow spontaneous beats to develop. The lower than normal rate of compression was recommended in order to allow the ventricles to fill and because one is attempting to elicit a subnormal rate of beat, namely, the rate at which the arrested heart would start beating again. A rapid returning heart beat probably is the result of massage plus epinephrine. Gunn further emphasized that massage is used to stimulate the heart and maintain circulation, but the most important thing is stimulation of the heart. In the excitement of the moment, mechanical stimulation of the heart can be overdone. One should frequently stop and watch for the first feeble heart beats. If these do not improve, then help must be supplied at intervals, and it is here that drug therapy may be of aid. It has been noted that occasionally with the first attempts at respiration the heart may suddenly stop permanently. The possible cause is that with the return of respiratory activity there is a return of other medullary centers to action, which may result in a sudden burst of vagus activity. This is one of the reasons for combining procaine with epinephrine since it may aid in offering protection against this complication. In our experience, procaine and epinephrine appear to be of real value in treating cardiac arrest. Epinephrine is usually the first drug thought of in any circulatory emergency. Since this drug may produce ventricular fibrillation it must be used with caution and never in large doses (not , more than 0.5 cc. of a 1 to 1000 solution). On two occasions we have seen the heart beating with no palpable pulse or audible blood pressure. It is likely that in some of the cases diagnosed as cardiac arrest an actual asystole may not exist. When there is a sudden disappearance of pulse with no demonstrable blood pressure, however, we do not hesitate to make the diagnosis of cardiac arrest and to administer epinephrine in small doses combined with procaine. This has been done with full awareness of the propensity of epinephrine to cause arrhythmias and possibly ventricular fibrillation. This procedure has been followed in all of our cases and while in some of the cases cardiac action has been restored too late to preserve normal cerebration, in none of the cases have we failed to restore cardiac beat. The value of drug therapy in cardiac arrest seems to be that it strengthens the effect of cardiac massage. It is wise to have ready in the operating room a kit containing a long cardiac needle, two 5 cc. syringes, two
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20 gauge needles and one ampule containing epinephrine 1 to 1000 and two ampules each containing 6 cc. of procaine 1 per cent. A modification of our treatment in this emergency has been suggested and tried by Dr. Lahey. When the cardiac arrest occurs, the cardiac needle not attached to a syringe should be inserted immediately by the surgeon. This maneuver will tell whether or not the heart is actually beating and in rare instances it may provide the stimulus to start cardiac activity again. Meanwhile, an operating room assistant should be drawing 4.75 cc. of procaine 1 per cent and 0.25 cc. of epinephrine 1 to 1000 in one syringe. This should be given to the surgeon immediately so that he can inject it. While this is being done, the second syringe can be made ready in a similar manner. No time should be wasted if needles and syringes and solutions are not ready. In that event, cardiac massage should be begun immediately and the solutions used when they are ready. If there is no response in three to five minutes to cardiac massage and the first injection, the second should be administered. Following this, procaine may be administered in a continuous intravenous drip through a vein in the arm or leg. Epinephrine, however, should probably not be repeated. The plan presented here has gradually evolved from experience with 15 cases of sudden cardiac arrest. All hearts were revived. Seven of these patients are alive and well. Seven patients died following varying periods of unconsciousness with evidence of severe brain damage. One patient recovered from his cardiac arrest only to succumb the following day to a coronary occlusion.
SUMMARY Some of the circulatory emergencies which affect the anesthesiologist require careful choice of anesthetic agents. Emergencies which occur during anesthesia require prompt and efficient treatment. Such treatment is greatly facilitated by trying to anticipate the possible acute circulatory complications which may occur and being prepared to treat them.
REFERENCES 1. Burstein, C. L.: Fundamental considerations in anesthesia. New York, Mac-
millan Company, 1949. 2. Cullen, S. C.: Anesthesia in general practice. Chicago, The Year Book Publishers, 1946. 3. Gunn, J. A.: Massage of heart and resuscitation. Brit. M. J. 1:9 (Jan. 1) 1921. 4. Lahey, F. H. and Eversole, U. H.: Differentiation of hypersensitive carotid sinus reflex and cardiac arrest on the operating table. Lahey Clin. Bull. (tn press) 5. Lahey, F. H. and Ruzicka, E. R.: Experiences with cardiac arrest. Surg., Gynec. & Obst. 90:108-118 (Jan.) 1950. 6. Melville, K. I.: Combined ephedrine-pituitary extract (posterior lobe) therapy in histamine shock. J. Pharmacol. & Exper. Therap. 44:279-293 (Mar.) 1932. 7. Raginsky, B. B.: The present status of analeptics in anesthesia. Tr. Internat. CoIl. Surgeons 1 :66-71 (July) 1938. 8. Ruzicka, E. R. and Eversole, U. H.: The carotid sinus in anesthesiology: report of two cases. Lahey Clin. Bull. 3:47-54 (Oct.) 1942.
• DRUG POISONING ALBERT
F.
GIGOT
IN overdosage, many drugs become poisons. Different agents kill by attacking different systems of the body. Toxicologists are familiar with the effect of cyanide on cellular metabolism, of carbon monoxide on hemoglobin efficiency, of mercury on the kidney, of strong acids and caustics on any tissue they contact, and of morphine and barbiturates on brain function. Agents depressing the central nervous system seem to fall more directly into the sphere of the anesthesiologist than do the others. Therefore, this paper will be confined to a discussion of intoxication with these drugs. The barbiturates are to be featured for two reasons: (1) they are involved with increasing frequency in cases of drug poisoning, and (2) treatment described for them is applicable to overdoses of most depressants of the central nervous system. These include morphine and the other opiates, chloral, paraldehyde and the combination of any of these with ethyl alcohol. In a gratifying percentage of cases treatment is successful even though the identity of the drug is not determined. When grading the steps in the handling of these cases top priority is given to the maintenance of a free airway and general, suppqrtive care of the patient. Next, there is the attempted diagnosis of the poison. Attention may then be directed to antidotes specific for that particular agent. CLINICAL PICTURE
A person who has had too much barbiturate presents this picture. He is comatose, and the minute volume of respiration is reduced. These two signs are constant. The rate of breathing is usually subnormal, although it may be accelerated. However, the depth of respiration is almost always quite shallow. Apart from the sensorium, the respiratory center of the brain appears to receive the greatest insult. Some degree of cyanosis may be present. If the blood concentration of the drug rises to a sufficient level, breathing will stop completely. The pupils may be contracted or dilated, or may display hippus, that is, alternate widening and narrowing. The blood circulation may be less efficient than normal. However, compared to the effect on respiration, the cardiovascular system withstands the abuse fairly well. In mild cases the blood pressure and pulse are not altered. As depression deepens they begin to show changes. The pulse pressure is lowered and the pulse rate accelerates. The blood pressure falls. A shock level may be reached when the poison has been overwhelming. In this state the skin is pallid and damp. The phenomenon of unconsciousness is not necessarily injurious; the effects of inadequate pulmonary ventilation create a greater danger. Insufficient aeration produces tissue hypoxia. The brain, first organ 719
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affected by oxygen-want, undergoes changes which in a few minutes are irreversible. This damage, as it occurs, deepens the stupor and further raises the threshold of the respiratory center to stimulation. Correction of this hypoxia, then, is the keystone of treatment. TREATMENT
Based on depth of intoxication, poison victims may be divided into two groups. Those in the first category are persons who, though comatose, are breathing well enough to satisfy their own oxygen demands. Those in the second division, also stuporous, do not have adequate pulmonary ventilation. They mayor may not show signs of cardiovascular distress.
Comatose Patients with Shallow Respiration but Sufficient to Satisfy Oxygen Demands.-In considering patients in the first category, stopping further absorption of the toxic agent is of first importance. A large stomach tube is passed, the organ emptied and then lavaged with water or saline. Very frequently fragments of gelatin capsules will be found, suggesting the diagnosis. At any rate the gastric contents should be saved for laboratory analysis. It is an advantage to carry out this procedure with the patient in moderate Trendelenburg position. Should regurgitation or vomiting occur this will tend to obviate aspiration of any fluid. Some toxicologists leave a dose of magnesium sulfate in the stomach with the intent of purging what barbiturate still lingers in the bowel. Others believe that the stomach should be left empty to preclude subsequent vomiting and aspiration. The judicious use of intravenous fluids is a further step in the treat~ ment. The word "judicious" is used with special reference to pulmonary edema. The patient who is immobile in bed and who is breathing very shallowly is prone to develop some degree of pulmonary edema. This may be precipitated by giving too much fluid or too much salt. It has been found that a person can get along quite well for a day or two without added saline. Fluids given are designed to maintain tissue hydration and to aid nutrition. Five per cent dextrose in water is probably the most useful fluid. In governing the dose of intravenous solution it is probably better to err on the side of underhydration rather than overhydration. A periodic check of the bladder is maintained and catheterization carried out when necessary. The patient should be turned frequently from side to side to discourage any edema which might be trying to creep into the dependent areas of the lungs. Once these steps in treatment have been instituted there is another precaution to be taken. There may be further absorption of barbiturates from the intestine. If this occurs the stupor and respiratory depression will deepen. Such an occurrence may demand a more vigorous type of therapy, the type used for patients having inadequate pulmonary ventilation. This leads to a discussion of the second category of cases.
Stuporous Patients without Adequate Pulmonary Ventilation.Patients in the first group are comatose and breathing shallowly, but
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display little else. The second division of those poisoned may be typified thusly: they are more depressed; breathing is so shallow and slow that cyanosis is frequently present. Cardiovascular function is often impaired, with a resultant weak, rapid pulse and lowered blood pressure. The skin may be cold and moist, evidencing a degree of shock. The extent of pulmonary ventilation is incompatible with tissue vitality, and this, apparently, is the serious feature in these cases. Correction of this condition is the first step in treatment. Artificial Respiration.-Before anything else is done every effort should be made to oxygenate the patient. Methods of doing this vary according to the facilities available. The method most at hand is manual artificial respiration.s Perhaps the prone technic of Schafer and the supine technic of Sylvester are the most widely used. The Sylvester method is reputed to provide a greater gaseous· exchange than the Schafer, but with the former, the patient is lying on his back and there is greater opportunity for obstruction of the pharynx with tongue or epiglottis. When no equipment is available for artificial respiration, mouth-to-mouth breathing is often of considerable benefit. Sustained, mechanical artificial respiration can be provided by the Drinker apparatus. Under trained supervision this method accomplishes its purpose very well. Careful regulation is necessary, for if the negative pressure is too great, subcutaneous emphysema may develop. If ventilation is too vigorous tetany may resultS owing to excessive elimination of carbon dioxide with subsequent tipping of the acid-base balance of the blood to the alkaline side. 2 Administration of Oxygen.-As well as benefiting from artificially increased amplitude of ventilation, the patient will also be aided by exposure to a high concentration of oxygen. This may be achieved with the use of an oxygen tent which, however, is valueless unless pulmonary exchange is adequate. Nasopharyngeal insuffla'tion is another effective method. A catheter, about 14 French in size, is passed through the nostril for a distance roughly equal to that between the tip of the nose and the tragus of the ear. The distal end of the catheter will be suspended in the back of the oropharynx. In the oxygen line a water bottle is interposed so that the gas bubbles through it for humidification. The maintenance of a physiologic plane of respiration with a gas machine is the most efficient technic, although it requires the services of an anesthesiologist. With this method one can control the patency of the patient's airway, remove any tracheobronchial secretions, direct the rate and volume of breathing and regulate the concentration of gases the patient receives. Under direct laryngoscopy an endotracheal tube is introduced after a preliminary spraying of the pharynx and larynx with 10 per cent cocaine if the reflexes are active, then a mask is placed over the face and 100 per cent oxygen is delivered to the patient from the gas machine. The tube should be removed, cleaned and reinserted every eight or ten hours. Certain advantages will accrue from the use of an endotracheal tube fitted with a balloon cuff.10 This cuff when inflated seals off the tracheal lumen surrounding the tube and
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prevents aspiration of any regurgitated gastric contents. The tube can be adapted to the conduits of the gas machine, so that the oxygen can flow only into the lungs. When the face mask is used over an un cuffed tube, gases may be blown down the esophagus to distend the stomach. Artificial respiration is carried out by the anesthesiologist compressing the rebreathing bag rhythmically. Carbon dioxide from the lungs is removed in the soda-lime filter. Excesses of this gas are not allowed to accumulate, and none is added to the circuit for the purpose of respiratory stimulation, for the patient is not suffering from lack of carbon dioxide with which to increase ventilation. The profound depression of the respiratory center in the brain so elevates its threshold that it is unresponsive to the carbon dioxide already present. 1 If facilities for tracheal intubation are not at hand an oropharyngeal or nasal airway may be employed. Miscellaneous Measures.-The procedure described will usually bring about adequate aeration of the lungs. Probably not until this point has been reached is it wise to institute other therapeutic measures. As mentioned earlier, Trendelenburg position is used so that gravity will inhibit aspiration of any regurgitated fluid. Mucus and saliva may readily be removed through a suction catheter fed into the endotracheal tube. Gastric lavage is then employed to remove any poison still retained in the stomach. Again, proper water balance and nutrition are striven for, with the emphasis on underhydration and a low salt intake. If the blood pressure is at a shock level intramuscular injections of ephedrine or methedrine are useful. A continuous intravenous drip of a vasopressor drug is more easily controlled. For example, 5 or 10 mg. of neosynephrine in one-half liter of intravenous solution can be delivered at a rate calculated to keep the pressure within normal limits. Change in position is helpful in repelling pulmonary edema. The patient should be rolled onto his opposite side at frequent intervals. Treatment of Complications.-Once treatment of the intoxication has been established, one should be on the alert for certain complications. It is important that the patient be under constant medical surveillance. The complications to watch for include: (1) aspiration of vomitus or tracheobronchial secretions, (2) hypoxia, (3) deepening depression and (4) pulmonary edema. Treatment of the first three conditions has been described. Edema of the lungs is a hypostatic phenomenon, the result of a relatively low intra-alveolar tension wherein serum transudate leaves the pulmonary capillaries and enters the alveoli. The proper maintenance of respiration and circulation will help to ward it off, and to reduce it if edema has already developed. Postural change in bed and the prudent administration of intravenous fluids and salt are useful adjuncts. Controlled respiration when breathing is very shallow has been described. In recent years this type of artificial respiration has been reinforced with technics of controlled positive pressure. Methods are available for applying positive pressure to both the inspiratory and the expiratory phases. Dillon 4 uses intermittent positive pressure respiration of a
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supplementary type. He has found that increasing the ventilation and establishing a favorable pressure pattern in the lungs usually control the problem of pulmonary edema so frequently seen. Use of Specific Antidotes and Nerve Stimulants.-The importance of controlled respiration and general supportive measures cannot be overemphasized. Few will question their value. The usefulness of specific antidotes and nerve stimulants, however, is constantly under debate. Popular analeptics include picrotoxin, metrazol, coramine, benzedrine and caffeine. These drugs all act to excite the central nervous system. Their effects on respiration are mediated through stimulation of the appropriate centers in the brain stem. It appears that tissue damage resulting from the stupor is due to the depression of respiration primarily, and circulation secondarily. The convulsants, for example, picrotoxin or metrazol, mayor may not improve the patient's condition and hasten recovery. They are not demanded for pulmonary or circulatory function. These systems may be controlled as already described with oxygen therapy and vasopressor drugs. The patient's return to consciousness depends on the destruction of the barbiturate, and it is the body itself which detoxifies and eliminates the poison. Proof is not available that any of the analeptics aid the breakdown of the depressant drugs. Without hastening the breakdown of the poison and its disappearance from the blood stream it is difficult to see how the convulsants can shorten the recovery period. A side effect of the analeptics on the central nervous system deserves consideration. In drug depression the brain is receivi,ng a reduced supply of oxygen. By increasing the rate of metabolism in nerve tissue it would seem that the convulsant drugs reduce still further the amount of oxygen available to the brain cells. There are many reports on the use of analeptics in the treatment of barbiturate poisoning. Picrotoxin is the drug which appears to be enjoying the most favor. In 1946 Boyd3 stated that "picrotoxin does not directly neutralize the toxic effects of barbiturates; rather it keeps the patient alive until all or most of the depressant drug has been oxidized or eliminated from the body. Thus, for example, picrotoxin does not awaken the patient in barbiturate coma; that does not occur until the excess barbiturate has been taken care of by the body." Its convulsant effect on the medulla oblongata is used to offset the depression from the barbiturate. In the method Boyd described picrotoxin is dissolved in saline, 1 mg. per cubic centimeter, and the solution given by slow intravenous drip, about 1 cc. each minute. The rate of flow is adjusted to keep the patient breathing deeply and the pulse and blood pressure satisfactory. If twitchings or convulsions occur the drip is slowed, but not stopped. This administration of picrotoxin calls for the constant attendance of a physician. Metrazol is often used, though it is somewhat less popular than picrotoxin. Freireich and Landsberg found benzedrine sulfate useful in treating acute barbiturate poisoning. 7
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Mousel and Essex9 studied the effects of respiratory stimulants on animals under pentothal sodium anesthesia. They found coramine, metrazol and picrotoxin to be without value in treating severe depression in dogs, cats and rabbits. Sodium succinate has been given repeated trials in the treatment of barbiturate intoxication. Pinschmidt, Ramsey and Haagll found this agent to be of little or no benefit in animals depressed by sodium pentobarbital. Recent studies13 in man have given equivocal results. In 1949 Seldon and his co-workers12 reported the use of human serum albumin in the treatment of barbiturate depression. They postulated that "permanent damage to the brain as a result of acute cerebral anoxia not only is a function of the duration of the anoxic period, but also, in the case of sublethal periods of anoxia must be conditioned by the duration and severity of a period of postanoxic cerebral edema." Therapy is directed toward this cerebral edema. They suggested intravenous administration of 25 per cent human serum albumin at frequent intervals. The 2 patients they so treated showed immediate improvement and ultimately complete recovery. Our inadequate knowledge of the fate of barbiturates in the body has made the choice of treatment a difficult one. The effects of various analeptics and other antidotes have been judged largely on clinical impressions rather than on biochemical data. Without paralleling the administration of curative agents by studies of blood concentrations of the poisons, the values of different treatments tend to be conjectural rather than factual. Very recently Fisher and his associates6 • 14 have described the quantitative estimation of barbiturates in blood by ultraviolet spectrophotometry. This has made feasible the rapid and accurate determination of barbiturate levels in blood and tissue. It makes possible for the first time the ready determination of the blood barbiturate concentration of a comatose patient. 5 Free use of this analytical method in the future should make for a more accurate interpretation of the results of treatment. REFERENCES 1. Ausherman, H. M.: Misconceptions regarding use of carbon dioxide in treatment of respiratory depression and asphyxia. Anesth. and Analg. 27: 172-175 (May-June) 1948. 2. Best, C. H. and Taylor, N. B.: The physiological basis of medical practice. A University of Toronto text in applied physiology. Ed. 4, Baltimore, Williams and Wilkins Co., 1945, pp. 1169. 3. Boyd, E. M.: Picrotoxin for barbiturate poisoning. Canad. M. A. J. 54:442443 (May) 1946. 4. Dillon, J. B.: Personal communication. 5. Fisher, R. S.: Barbiturate toxicity. New England J. Med. 240:395-396 (March 10) 1949. 6. Fisher, R. S., Walker, J. T. and Plummer, C. W.: Quantitative estimation of barbiturates in blood by ultra-violet spectrophotometry; experimental and clinical results. Am. J. Clin. Path. 18:462-469 (June) 1948. 7. Freireich, A. W. and Landsberg, J. W.: Amphetamine (benzedrine) sulphate for acute barbiturate poisoning. J.A.M.A. 131:661-663 (June 22) 1946.
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8. Leigh, M. D. and Richardson, F. M.: Oxygen therapy and resuscitation. Canad. M. A. J. 47:555-561 (Dec.) 1942. 9. Mousel, L. H. and Essex, H. E.: Experimental study of effects of respiratory stimulants in animals under pentothal sodium anesthesia. Anesthesiology 2:272-280 (May) 1941. 10. Nicholson, M. J.: Technic of endotracheal anesthesia. S. Clin. North America 29:941-961 (June) 1949. 11. Pinschmidt, N. W., Ramsey, H. and Haag, H. B.: Studies on antagonism of sodium succinate to barbiturate depression. J. Pharm. and Exper. Therap. 83:45-52 (Jan.) 1945. 12. Seldon, T. H., Faulconer, A., Jr., Courtin, R. F. and Pino, D. M.: Postanesthetic encephalopathy; the postulation of cerebral edema as a basis for rational treatment. Proc. Staff Meet., Mayo Clin. 24:370-374 (July 6) 1949. 13. Tucci, J. H., Brazier, M. A. B., Miles, H. H. W. and Finesinger, J. E.: A study of pentothal sodium anesthesia and a critical investigation of the use of succinate as an antidote. Anesthesiology 10:25-39 (Jan.) 1949. 14. Walker, J. T., Fisher, R. S. and McHugh, J. J.: Quantitative estimation of barbiturates in blood by ultra-violet spectrophotometry; analytical method. Am. J. Clin. Path. 18:451-461 (June) 1948.
CHOICE OF ANESTHESIA
The choice of anesthesia for the patient who is hemorrhaging or in shock is general anesthesia or a combination of local and general anesthesia. When better relaxation of abdominal musculature is required, the need is met by using one of the muscle relaxing drugs, such as curare. Spinal anesthesia is not the anesthetic method of choice. Spinal anesthesia produces peripheral arteriolar and capillary dilatation because of the temporary paralysis of the sympathetic nerves. A great deal of blood 713
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EDWIN R. RUZICKA
consequently stagnates in these areas. The result is a reduced venous return to the heart, a diminished cardiac output and a fall in blood pressure. When this is superjmposed on a circulatory system already taxed to the utmost in an attempt to retain normal physiologic activity, the result may be disastrous. EMERGENCIES OCCURRING DURING INDUCTION OF ANESTHESIA
The accidental intravenous administration of a local anesthetic agent may produce alarming symptoms during the induction of local anesthesia. The patient may become apprehensive and nervous or become very quiet and lapse into unconsciousness. Other symptoms are pallor and increased perspiration. The patient may also show respiratory irregularities such as sighing, dyspnea and shallow breathing. The pulse is usually slow and poor in quality. Twitching may begin around the eyes and nose and develop into generalized convulsions. Treatment must begin immediately. No further attempt to administer the anesthetic should be made. Oxygen should be administered immediately. Intravenous barbiturates such as nembutal or pentothal should be given to minimize the symptoms or to stop convulsions when they occur. Vasopressor drugs should also be used in the treatment of hypotension if it develops. Another circulatory emergency occurring during the early stages of anesthesia is the accidental intra-arterial injection of barbiturate drugs. As soon as injection begins, the patient complains of intense searing pain in the arm and fingers. The skin of the hand and forearm usually becomes blanched and the radial pulse is not palpable. These are indications of a severe, widespread vasospasm of the blood vessels in the arm. The in~ jection of drug should be immediately discontinued. A stellate ganglion block on the same side should be done as quickly as possible. This will usually relieve the vasospasm and pain. It may be necessary to repeat the block two or three times on successive days. This treatment has a tendency to relieve vasospasm and may prevent thrombosis of the artery. EMERGENCIES ARISING AFTER ANESTHESIA HAS BEEN ESTABLISHED
The peripheral arteriolar and capillary dilatation which spinal anesthesia produces by temporarily paralyzing the sympathetic nerves may cuse hypotension. This may be dangerous in some patients and should always be considered unphysiologic. A systolic pressure of 80 mm. of mercury is usually considered the critical level for any patient. The individual must be considered, however, and anyone who has had a sustained hypertension for a long period of time should probably not be allowed to develop a systolic pressure of less than half the usual pressure. When it is thought desirable to be able to control the blood pressure as much as possible it is good practice to have constant intravenous fluids running. If it becomes necessary to raise the blood pressure, neosynephrine, 1 per cent, may be added to the solution. A satisfactory method to follow is to mix 1 cc. of neosynephrine with 500 cc. of fluid or 2 cc. of
ACUTE CIRCULATORY EMERGENCIES
715
neosynephrine with 1 liter of fluid. The blood pressure level may be regulated by manipulating the speed of flow of the prepared solution. This method of controlling the blood pressure may be carried over into the postoperative period with little or no trouble. N eosynephrine should never be added to a blood transfusion since the patient may need the blood badly but not need the stimulating effect of the neosynephrine. The neosynephrine solution may be added to the tubing through which the transfusion or other fluid is running by piercing the tubing with the needle of the neosynephrine set and taping the needle in place. The solutions may then be controlled independently of each other. The intravenous use of drugs to raise the blood pressure may not be necessary. Neosynephrine, 1 per cent, 2 minims, may be given subcutaneously or intramuscularly. Neosynephrine used in this manner has a tendency to raise the blood pressure rather markedly but the rise is not sustained. Melville and 'ater Raginsky suggested the intramuscular use of a mixture of 25 mg. of ephedrine and 5 units of pitressin. The blood pressure rise which results is not rapid but is sustained over a longer period of time than the blood pressure rise from neosynephrine. While vasopressor drugs are valuable for the support of blood pressure when the hypotension is due to the temporary paralysis of the sympathetic nerves by spinal anesthesia, they must never be used as substitutes for fluids or blood in surgical shock. Respiratory depression from any cause will initiate a chain of events which may result, among other things, in a marked hypotension. Too heavy premedication or overdosage of the anesthetic agent will cause inefficient respiratory movements. The inspiratory thoracic movement which brings blood into the great veins of the chest is impaired and the flow of blood into the right side of the heart is reduced. The result is inefficient cardiac action with a lessened outflow of blood and a fall in blood pressure. Decreased respiratory movements cause anoxemia and anoxic anoxia. The cerebral and medullary centers are then depressed because of oxygen lack. A vicious circle of deepening respiratory depression is thus instituted. The blood pressure fall which results from the changes produced by respiratory depression may be further aided by depression of the carotid sinus mechanism and the loss of its compensatory action. CAROTID SINUS REFLEX
It is important to bear in mind the possibility of a hypersensitive carotid sinus reflex whenever surgery of the neck is undertaken. The carotid sinus is located at the bifurcation of the common carotid artery on each side of the neck. Most anesthetic agents depress the carotid sinus but sometimes the application of pressure in the neck may start a severe circulatory reaction. This is seen, for example, during the course of a thyroidectomy when manipulation and pressure from retractors in the area of the carotid sinus may produce disappearance of the pulse and blood pressure or marked bradycardia and hypotension. Respiratory depression may occur at the same time but does not invariably do so.
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EDWIN R. RUZICKA
When this reaction occurs, packs and retractors should be removed and 1 per cent solution of procaine injected in the area of the bifurcation of the common carotid artery. The systemic blood pressure, pulse and respiration will return to normal in a few minutes and operation may be continued. This reaction can occur when the cervical abscess in Ludwig'S angina is incised. Safeguards against this reaction include the maintenance of a clear airway, avoidance of pressure on the neck and the use of atropine preoperatively to depress the parasympathetic nerves involved. CARDIAC ARREST
Sudden cardiac arrest may occur without warning during anesthesia. The surgeon is not usually the first to establish the diagnosis of cardiac arrest unless the operation he is doing is such that an artery is under direct vision and he notes cessation of pulsation in it. The anesthesiologist is most frequently the first to become awarl' of this complication. A constantly alert watch must be maintained for this condition by both the anesthesiologist and surgeon since cardiac arrest may occur at any time during the induction and maintenance of the anesthesia and at any stage of the operative procedure. The type of operation performed is of no assistance in anticipating or preventing sudden cardiac arrest since it may occur during any type of operative procedure. It may also occur with any anesthetic agent or combination of agents, including spinal anesthesia when used as the sole anesthetic method. The anesthesiologist must notify the surgeon as soon as the pulse and blood pressure disappear. If he even suspects that there has been a cardiac arrest, the surgeon must be asked to check arterial pulsations. False alarms will inevitably occur but must be tolerated. The short time during which treatment must be applied to be effective means that the anesthesiologist and surgeon cannot waste time in useless checking, but must be ready for instant decision and rapid institution, of emergency measures. A plan of action which we have presented before and see no reason as yet to change is as follows: (1) artificial respiration is started with 100 per cent oxygen; (2) cardiac massage is begun immediately by the surgeon-this is the all important step; (3) drug therapy is given consisting of the use of procaine and epinephrine, and (4) general methods of treatment are followed including the administration of intravenous fluids and the institution of 5 to 10 degree Trendelenburg position. Artificial respiration with 100 per cent oxygen presupposes that the airway is unobstructed. This may necessitate the insertion of an endotracheal tube. Artificial respiration with 100 per cent oxygen maintains a high concentration of oxygen in the alveoli and also may have some mechanical effect on maintenance of circulation. The return of cardiac activity does not always signal the immediate return of respiratory activity. It may be necessary to continue artificial respiration from a few minutes to several hours after the reappearance of cardiac activity. Artificial respiration is useless unless the circulation is maintained. Cardiac maSsage is the mainstay of treatment and must be started im-
• ACUTE CIRCULATORY EMERGENCIES
717
mediately if the outcome is to be favorable. The approach depends on the operative procedure but resolves itself into three routes: (1) transperitoneal subdiaphragmatic; (2) transperitoneal transdiaphragmatic, and (3) transthoracic. The rate of cardiac massage has been quoted at various figures. Many rates have been suggested but Gunn seems to have offered a really plausible figure with an explanation for his contention. He maintained that massage of the heart is not a question for indifference but that attention to detail is important. He even suggested practice for this maneuver. Gunn stated that compression should be gradual and relaxation abrupt, with rate of compression, at most, only half the normal rate. The massage must be interrupted at regular short intervals for a few seconds in order to allow spontaneous beats to develop. The lower than normal rate of compression was recommended in order to allow the ventricles to fill and because one is attempting to elicit a subnormal rate of beat, namely, the rate at which the arrested heart would start beating again. A rapid returning heart beat probably is the result of massage plus epinephrine. Gunn further emphasized that massage is used to stimulate the heart and maintain circulation, but the most important thing is stimulation of the heart. In the excitement of the moment, mechanical stimulation of the heart can be overdone. One should frequently stop and watch for the first feeble heart beats. If these do not improve, then help must be supplied at intervals, and it is here that drug therapy may be of aid. It has been noted that occasionally with the first attempts at respiration the heart may suddenly stop permanently. The possible cause is that with the return of respiratory activity there is a return of other medullary centers to action, which may result in a sudden burst of vagus activity. This is one of the reasons for combining procaine with epinephrine since it may aid in offering protection against this complication. In our experience, procaine and epinephrine appear to be of real value in treating cardiac arrest. Epinephrine is usually the first drug thought of in any circulatory emergency. Since this drug may produce ventricular fibrillation it must be used with caution and never in large doses (not , more than 0.5 cc. of a 1 to 1000 solution). On two occasions we have seen the heart beating with no palpable pulse or audible blood pressure. It is likely that in some of the cases diagnosed as cardiac arrest an actual asystole may not exist. When there is a sudden disappearance of pulse with no demonstrable blood pressure, however, we do not hesitate to make the diagnosis of cardiac arrest and to administer epinephrine in small doses combined with procaine. This has been done with full awareness of the propensity of epinephrine to cause arrhythmias and possibly ventricular fibrillation. This procedure has been followed in all of our cases and while in some of the cases cardiac action has been restored too late to preserve normal cerebration, in none of the cases have we failed to restore cardiac beat. The value of drug therapy in cardiac arrest seems to be that it strengthens the effect of cardiac massage. It is wise to have ready in the operating room a kit containing a long cardiac needle, two 5 cc. syringes, two
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20 gauge needles and one ampule containing epinephrine 1 to 1000 and two ampules each containing 6 cc. of procaine 1 per cent. A modification of our treatment in this emergency has been suggested and tried by Dr. Lahey. When the cardiac arrest occurs, the cardiac needle not attached to a syringe should be inserted immediately by the surgeon. This maneuver will tell whether or not the heart is actually beating and in rare instances it may provide the stimulus to start cardiac activity again. Meanwhile, an operating room assistant should be drawing 4.75 cc. of procaine 1 per cent and 0.25 cc. of epinephrine 1 to 1000 in one syringe. This should be given to the surgeon immediately so that he can inject it. While this is being done, the second syringe can be made ready in a similar manner. No time should be wasted if needles and syringes and solutions are not ready. In that event, cardiac massage should be begun immediately and the solutions used when they are ready. If there is no response in three to five minutes to cardiac massage and the first injection, the second should be administered. Following this, procaine may be administered in a continuous intravenous drip through a vein in the arm or leg. Epinephrine, however, should probably not be repeated. The plan presented here has gradually evolved from experience with 15 cases of sudden cardiac arrest. All hearts were revived. Seven of these patients are alive and well. Seven patients died following varying periods of unconsciousness with evidence of severe brain damage. One patient recovered from his cardiac arrest only to succumb the following day to a coronary occlusion.
SUMMARY Some of the circulatory emergencies which affect the anesthesiologist require careful choice of anesthetic agents. Emergencies which occur during anesthesia require prompt and efficient treatment. Such treatment is greatly facilitated by trying to anticipate the possible acute circulatory complications which may occur and being prepared to treat them.
REFERENCES 1. Burstein, C. L.: Fundamental considerations in anesthesia. New York, Mac-
millan Company, 1949. 2. Cullen, S. C.: Anesthesia in general practice. Chicago, The Year Book Publishers, 1946. 3. Gunn, J. A.: Massage of heart and resuscitation. Brit. M. J. 1:9 (Jan. 1) 1921. 4. Lahey, F. H. and Eversole, U. H.: Differentiation of hypersensitive carotid sinus reflex and cardiac arrest on the operating table. Lahey Clin. Bull. (tn press) 5. Lahey, F. H. and Ruzicka, E. R.: Experiences with cardiac arrest. Surg., Gynec. & Obst. 90:108-118 (Jan.) 1950. 6. Melville, K. I.: Combined ephedrine-pituitary extract (posterior lobe) therapy in histamine shock. J. Pharmacol. & Exper. Therap. 44:279-293 (Mar.) 1932. 7. Raginsky, B. B.: The present status of analeptics in anesthesia. Tr. Internat. CoIl. Surgeons 1 :66-71 (July) 1938. 8. Ruzicka, E. R. and Eversole, U. H.: The carotid sinus in anesthesiology: report of two cases. Lahey Clin. Bull. 3:47-54 (Oct.) 1942.
• DRUG POISONING ALBERT
F.
GIGOT
IN overdosage, many drugs become poisons. Different agents kill by attacking different systems of the body. Toxicologists are familiar with the effect of cyanide on cellular metabolism, of carbon monoxide on hemoglobin efficiency, of mercury on the kidney, of strong acids and caustics on any tissue they contact, and of morphine and barbiturates on brain function. Agents depressing the central nervous system seem to fall more directly into the sphere of the anesthesiologist than do the others. Therefore, this paper will be confined to a discussion of intoxication with these drugs. The barbiturates are to be featured for two reasons: (1) they are involved with increasing frequency in cases of drug poisoning, and (2) treatment described for them is applicable to overdoses of most depressants of the central nervous system. These include morphine and the other opiates, chloral, paraldehyde and the combination of any of these with ethyl alcohol. In a gratifying percentage of cases treatment is successful even though the identity of the drug is not determined. When grading the steps in the handling of these cases top priority is given to the maintenance of a free airway and general, suppqrtive care of the patient. Next, there is the attempted diagnosis of the poison. Attention may then be directed to antidotes specific for that particular agent. CLINICAL PICTURE
A person who has had too much barbiturate presents this picture. He is comatose, and the minute volume of respiration is reduced. These two signs are constant. The rate of breathing is usually subnormal, although it may be accelerated. However, the depth of respiration is almost always quite shallow. Apart from the sensorium, the respiratory center of the brain appears to receive the greatest insult. Some degree of cyanosis may be present. If the blood concentration of the drug rises to a sufficient level, breathing will stop completely. The pupils may be contracted or dilated, or may display hippus, that is, alternate widening and narrowing. The blood circulation may be less efficient than normal. However, compared to the effect on respiration, the cardiovascular system withstands the abuse fairly well. In mild cases the blood pressure and pulse are not altered. As depression deepens they begin to show changes. The pulse pressure is lowered and the pulse rate accelerates. The blood pressure falls. A shock level may be reached when the poison has been overwhelming. In this state the skin is pallid and damp. The phenomenon of unconsciousness is not necessarily injurious; the effects of inadequate pulmonary ventilation create a greater danger. Insufficient aeration produces tissue hypoxia. The brain, first organ 719
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ALBERT F. GIGOT
affected by oxygen-want, undergoes changes which in a few minutes are irreversible. This damage, as it occurs, deepens the stupor and further raises the threshold of the respiratory center to stimulation. Correction of this hypoxia, then, is the keystone of treatment. TREATMENT
Based on depth of intoxication, poison victims may be divided into two groups. Those in the first category are persons who, though comatose, are breathing well enough to satisfy their own oxygen demands. Those in the second division, also stuporous, do not have adequate pulmonary ventilation. They mayor may not show signs of cardiovascular distress.
Comatose Patients with Shallow Respiration but Sufficient to Satisfy Oxygen Demands.-In considering patients in the first category, stopping further absorption of the toxic agent is of first importance. A large stomach tube is passed, the organ emptied and then lavaged with water or saline. Very frequently fragments of gelatin capsules will be found, suggesting the diagnosis. At any rate the gastric contents should be saved for laboratory analysis. It is an advantage to carry out this procedure with the patient in moderate Trendelenburg position. Should regurgitation or vomiting occur this will tend to obviate aspiration of any fluid. Some toxicologists leave a dose of magnesium sulfate in the stomach with the intent of purging what barbiturate still lingers in the bowel. Others believe that the stomach should be left empty to preclude subsequent vomiting and aspiration. The judicious use of intravenous fluids is a further step in the treat~ ment. The word "judicious" is used with special reference to pulmonary edema. The patient who is immobile in bed and who is breathing very shallowly is prone to develop some degree of pulmonary edema. This may be precipitated by giving too much fluid or too much salt. It has been found that a person can get along quite well for a day or two without added saline. Fluids given are designed to maintain tissue hydration and to aid nutrition. Five per cent dextrose in water is probably the most useful fluid. In governing the dose of intravenous solution it is probably better to err on the side of underhydration rather than overhydration. A periodic check of the bladder is maintained and catheterization carried out when necessary. The patient should be turned frequently from side to side to discourage any edema which might be trying to creep into the dependent areas of the lungs. Once these steps in treatment have been instituted there is another precaution to be taken. There may be further absorption of barbiturates from the intestine. If this occurs the stupor and respiratory depression will deepen. Such an occurrence may demand a more vigorous type of therapy, the type used for patients having inadequate pulmonary ventilation. This leads to a discussion of the second category of cases.
Stuporous Patients without Adequate Pulmonary Ventilation.Patients in the first group are comatose and breathing shallowly, but
DRUG POISONING
721
display little else. The second division of those poisoned may be typified thusly: they are more depressed; breathing is so shallow and slow that cyanosis is frequently present. Cardiovascular function is often impaired, with a resultant weak, rapid pulse and lowered blood pressure. The skin may be cold and moist, evidencing a degree of shock. The extent of pulmonary ventilation is incompatible with tissue vitality, and this, apparently, is the serious feature in these cases. Correction of this condition is the first step in treatment. Artificial Respiration.-Before anything else is done every effort should be made to oxygenate the patient. Methods of doing this vary according to the facilities available. The method most at hand is manual artificial respiration.s Perhaps the prone technic of Schafer and the supine technic of Sylvester are the most widely used. The Sylvester method is reputed to provide a greater gaseous· exchange than the Schafer, but with the former, the patient is lying on his back and there is greater opportunity for obstruction of the pharynx with tongue or epiglottis. When no equipment is available for artificial respiration, mouth-to-mouth breathing is often of considerable benefit. Sustained, mechanical artificial respiration can be provided by the Drinker apparatus. Under trained supervision this method accomplishes its purpose very well. Careful regulation is necessary, for if the negative pressure is too great, subcutaneous emphysema may develop. If ventilation is too vigorous tetany may resultS owing to excessive elimination of carbon dioxide with subsequent tipping of the acid-base balance of the blood to the alkaline side. 2 Administration of Oxygen.-As well as benefiting from artificially increased amplitude of ventilation, the patient will also be aided by exposure to a high concentration of oxygen. This may be achieved with the use of an oxygen tent which, however, is valueless unless pulmonary exchange is adequate. Nasopharyngeal insuffla'tion is another effective method. A catheter, about 14 French in size, is passed through the nostril for a distance roughly equal to that between the tip of the nose and the tragus of the ear. The distal end of the catheter will be suspended in the back of the oropharynx. In the oxygen line a water bottle is interposed so that the gas bubbles through it for humidification. The maintenance of a physiologic plane of respiration with a gas machine is the most efficient technic, although it requires the services of an anesthesiologist. With this method one can control the patency of the patient's airway, remove any tracheobronchial secretions, direct the rate and volume of breathing and regulate the concentration of gases the patient receives. Under direct laryngoscopy an endotracheal tube is introduced after a preliminary spraying of the pharynx and larynx with 10 per cent cocaine if the reflexes are active, then a mask is placed over the face and 100 per cent oxygen is delivered to the patient from the gas machine. The tube should be removed, cleaned and reinserted every eight or ten hours. Certain advantages will accrue from the use of an endotracheal tube fitted with a balloon cuff.10 This cuff when inflated seals off the tracheal lumen surrounding the tube and
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ALBERT F. GIGOT
prevents aspiration of any regurgitated gastric contents. The tube can be adapted to the conduits of the gas machine, so that the oxygen can flow only into the lungs. When the face mask is used over an un cuffed tube, gases may be blown down the esophagus to distend the stomach. Artificial respiration is carried out by the anesthesiologist compressing the rebreathing bag rhythmically. Carbon dioxide from the lungs is removed in the soda-lime filter. Excesses of this gas are not allowed to accumulate, and none is added to the circuit for the purpose of respiratory stimulation, for the patient is not suffering from lack of carbon dioxide with which to increase ventilation. The profound depression of the respiratory center in the brain so elevates its threshold that it is unresponsive to the carbon dioxide already present. 1 If facilities for tracheal intubation are not at hand an oropharyngeal or nasal airway may be employed. Miscellaneous Measures.-The procedure described will usually bring about adequate aeration of the lungs. Probably not until this point has been reached is it wise to institute other therapeutic measures. As mentioned earlier, Trendelenburg position is used so that gravity will inhibit aspiration of any regurgitated fluid. Mucus and saliva may readily be removed through a suction catheter fed into the endotracheal tube. Gastric lavage is then employed to remove any poison still retained in the stomach. Again, proper water balance and nutrition are striven for, with the emphasis on underhydration and a low salt intake. If the blood pressure is at a shock level intramuscular injections of ephedrine or methedrine are useful. A continuous intravenous drip of a vasopressor drug is more easily controlled. For example, 5 or 10 mg. of neosynephrine in one-half liter of intravenous solution can be delivered at a rate calculated to keep the pressure within normal limits. Change in position is helpful in repelling pulmonary edema. The patient should be rolled onto his opposite side at frequent intervals. Treatment of Complications.-Once treatment of the intoxication has been established, one should be on the alert for certain complications. It is important that the patient be under constant medical surveillance. The complications to watch for include: (1) aspiration of vomitus or tracheobronchial secretions, (2) hypoxia, (3) deepening depression and (4) pulmonary edema. Treatment of the first three conditions has been described. Edema of the lungs is a hypostatic phenomenon, the result of a relatively low intra-alveolar tension wherein serum transudate leaves the pulmonary capillaries and enters the alveoli. The proper maintenance of respiration and circulation will help to ward it off, and to reduce it if edema has already developed. Postural change in bed and the prudent administration of intravenous fluids and salt are useful adjuncts. Controlled respiration when breathing is very shallow has been described. In recent years this type of artificial respiration has been reinforced with technics of controlled positive pressure. Methods are available for applying positive pressure to both the inspiratory and the expiratory phases. Dillon 4 uses intermittent positive pressure respiration of a
DRUG POISONING
723
supplementary type. He has found that increasing the ventilation and establishing a favorable pressure pattern in the lungs usually control the problem of pulmonary edema so frequently seen. Use of Specific Antidotes and Nerve Stimulants.-The importance of controlled respiration and general supportive measures cannot be overemphasized. Few will question their value. The usefulness of specific antidotes and nerve stimulants, however, is constantly under debate. Popular analeptics include picrotoxin, metrazol, coramine, benzedrine and caffeine. These drugs all act to excite the central nervous system. Their effects on respiration are mediated through stimulation of the appropriate centers in the brain stem. It appears that tissue damage resulting from the stupor is due to the depression of respiration primarily, and circulation secondarily. The convulsants, for example, picrotoxin or metrazol, mayor may not improve the patient's condition and hasten recovery. They are not demanded for pulmonary or circulatory function. These systems may be controlled as already described with oxygen therapy and vasopressor drugs. The patient's return to consciousness depends on the destruction of the barbiturate, and it is the body itself which detoxifies and eliminates the poison. Proof is not available that any of the analeptics aid the breakdown of the depressant drugs. Without hastening the breakdown of the poison and its disappearance from the blood stream it is difficult to see how the convulsants can shorten the recovery period. A side effect of the analeptics on the central nervous system deserves consideration. In drug depression the brain is receivi,ng a reduced supply of oxygen. By increasing the rate of metabolism in nerve tissue it would seem that the convulsant drugs reduce still further the amount of oxygen available to the brain cells. There are many reports on the use of analeptics in the treatment of barbiturate poisoning. Picrotoxin is the drug which appears to be enjoying the most favor. In 1946 Boyd3 stated that "picrotoxin does not directly neutralize the toxic effects of barbiturates; rather it keeps the patient alive until all or most of the depressant drug has been oxidized or eliminated from the body. Thus, for example, picrotoxin does not awaken the patient in barbiturate coma; that does not occur until the excess barbiturate has been taken care of by the body." Its convulsant effect on the medulla oblongata is used to offset the depression from the barbiturate. In the method Boyd described picrotoxin is dissolved in saline, 1 mg. per cubic centimeter, and the solution given by slow intravenous drip, about 1 cc. each minute. The rate of flow is adjusted to keep the patient breathing deeply and the pulse and blood pressure satisfactory. If twitchings or convulsions occur the drip is slowed, but not stopped. This administration of picrotoxin calls for the constant attendance of a physician. Metrazol is often used, though it is somewhat less popular than picrotoxin. Freireich and Landsberg found benzedrine sulfate useful in treating acute barbiturate poisoning. 7
724
ALBERT F. GIGOT
Mousel and Essex9 studied the effects of respiratory stimulants on animals under pentothal sodium anesthesia. They found coramine, metrazol and picrotoxin to be without value in treating severe depression in dogs, cats and rabbits. Sodium succinate has been given repeated trials in the treatment of barbiturate intoxication. Pinschmidt, Ramsey and Haagll found this agent to be of little or no benefit in animals depressed by sodium pentobarbital. Recent studies13 in man have given equivocal results. In 1949 Seldon and his co-workers12 reported the use of human serum albumin in the treatment of barbiturate depression. They postulated that "permanent damage to the brain as a result of acute cerebral anoxia not only is a function of the duration of the anoxic period, but also, in the case of sublethal periods of anoxia must be conditioned by the duration and severity of a period of postanoxic cerebral edema." Therapy is directed toward this cerebral edema. They suggested intravenous administration of 25 per cent human serum albumin at frequent intervals. The 2 patients they so treated showed immediate improvement and ultimately complete recovery. Our inadequate knowledge of the fate of barbiturates in the body has made the choice of treatment a difficult one. The effects of various analeptics and other antidotes have been judged largely on clinical impressions rather than on biochemical data. Without paralleling the administration of curative agents by studies of blood concentrations of the poisons, the values of different treatments tend to be conjectural rather than factual. Very recently Fisher and his associates6 • 14 have described the quantitative estimation of barbiturates in blood by ultraviolet spectrophotometry. This has made feasible the rapid and accurate determination of barbiturate levels in blood and tissue. It makes possible for the first time the ready determination of the blood barbiturate concentration of a comatose patient. 5 Free use of this analytical method in the future should make for a more accurate interpretation of the results of treatment. REFERENCES 1. Ausherman, H. M.: Misconceptions regarding use of carbon dioxide in treatment of respiratory depression and asphyxia. Anesth. and Analg. 27: 172-175 (May-June) 1948. 2. Best, C. H. and Taylor, N. B.: The physiological basis of medical practice. A University of Toronto text in applied physiology. Ed. 4, Baltimore, Williams and Wilkins Co., 1945, pp. 1169. 3. Boyd, E. M.: Picrotoxin for barbiturate poisoning. Canad. M. A. J. 54:442443 (May) 1946. 4. Dillon, J. B.: Personal communication. 5. Fisher, R. S.: Barbiturate toxicity. New England J. Med. 240:395-396 (March 10) 1949. 6. Fisher, R. S., Walker, J. T. and Plummer, C. W.: Quantitative estimation of barbiturates in blood by ultra-violet spectrophotometry; experimental and clinical results. Am. J. Clin. Path. 18:462-469 (June) 1948. 7. Freireich, A. W. and Landsberg, J. W.: Amphetamine (benzedrine) sulphate for acute barbiturate poisoning. J.A.M.A. 131:661-663 (June 22) 1946.
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8. Leigh, M. D. and Richardson, F. M.: Oxygen therapy and resuscitation. Canad. M. A. J. 47:555-561 (Dec.) 1942. 9. Mousel, L. H. and Essex, H. E.: Experimental study of effects of respiratory stimulants in animals under pentothal sodium anesthesia. Anesthesiology 2:272-280 (May) 1941. 10. Nicholson, M. J.: Technic of endotracheal anesthesia. S. Clin. North America 29:941-961 (June) 1949. 11. Pinschmidt, N. W., Ramsey, H. and Haag, H. B.: Studies on antagonism of sodium succinate to barbiturate depression. J. Pharm. and Exper. Therap. 83:45-52 (Jan.) 1945. 12. Seldon, T. H., Faulconer, A., Jr., Courtin, R. F. and Pino, D. M.: Postanesthetic encephalopathy; the postulation of cerebral edema as a basis for rational treatment. Proc. Staff Meet., Mayo Clin. 24:370-374 (July 6) 1949. 13. Tucci, J. H., Brazier, M. A. B., Miles, H. H. W. and Finesinger, J. E.: A study of pentothal sodium anesthesia and a critical investigation of the use of succinate as an antidote. Anesthesiology 10:25-39 (Jan.) 1949. 14. Walker, J. T., Fisher, R. S. and McHugh, J. J.: Quantitative estimation of barbiturates in blood by ultra-violet spectrophotometry; analytical method. Am. J. Clin. Path. 18:451-461 (June) 1948.