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Some Attempts to Simplify the Treatment for Diabetes and Its Acute Complications
Some Attempts to Simplify the Treatment for Diabetes and Its Acute Complications GARFIELD G. DUNCAN, M.D., F.A.C.P.*
THE therapy for diabetes is not simple, but too often medical writings on this subject make it more complex than it need be in the light of present day knowledge. Too often details of study and therapy have been kept on the research level instead of being reduced to those essentials necessary for clinical application. It is my purpose to deal with plans of management of the diabetic patient which lend themselves to the most practical application and which are shorn of needless complexity, with the hope that they will be widely and effectively adopted. These plans deal with:
A. Detection of diabetes-a simplified means of identifying diabetes in doubtful cases B. Insulin therapy 1. Which patients do and which patients do not need to be given insulin 2. Plans of insulin therapy in the absence of acute complications C. The management of diabetes during acute complications D. Tests for ketonemia 1. A most reliable but little used test for the detection of diabetic coma at the bedside-a simple test for the degree of ketonemia. The value of this test is just beginning to receive the attention it deserves. 2. The degree of ketonemia as a guide in the treatment for diabetic coma DETECTION OF DIABETES
The diagnosis of diabetes is a simple matter when the classical symptoms, glycosuria and hyperglycemia, are present, in which case no further diagnostic studies are necessary. In individuals who exhibit none of these manifestations, but in whom diabetes may be suspected, a specimen of blood taken two hours after a liberal meal may have a sugar content above 170 mg. per 100 cc., and if so it usually indicates diabetes. Fasting blood sugar values are often normal in the presence of mild diabetes, hence the value of a postprandial test. ,.. Clinical Professor of Medicine, JejJerson Medical College; Director of the Medical Division8 of the Pennsylvania Hospital and the Benjamin Franklin Clinic. 1579
Garfield G. Duncan
1580
Glucose tolerance tests are indicated when the diabetes cannot be detected or ruled out without them. A simplified glucose tolerance test, which is mentioned in another paper in this symposium and which we have used as a screening test for six years at the Benjamin Franklin Clinic, comprises (a) the giving of 100 grams of glucose in a pint of water flavored with lemon and (b) taking a single specimen of venous blood two hours after the glucose is given. If the blood sugar value (Folin-Wu method) is below 120 mg. per 100 cc., one can safely conclude that there is no detectable evidence of diabetes. If the value exceeds 140 mg., the diagnosis of diabetes is indicated provided suitable precautions outlined by Parkhurst and Betsch (see p. 1572) are taken. Values between 120 and 140 mg. are inconclusive and the test should be repeated several weeks later. This simple diagnostic procedure is not so cumbersome as the usual glucose tolerance test, and I do not believe its simplicity sacrifices in the slightest its diagnostic value. Its simplicity should encourage widespread adoption, particularly in the screening of possible candidates for diabetes, notably overweight relatives of diabetic patients. INSULIN THERAPY
1. Which patients should be given and which should not be given insulin? The obese diabetic free from acute complications does not need insulin therapy. The diabetes is mild and usually will be controlled within two or three weeks if a reducing diet is adhered to. If insulin is given to these patients, they will attribute the control of the diabetes to the insulin and consider the diet to be of secondary importance. The result is that they rarely reduce weight appreciably and continue on insulin therapy indefinitely. To permit a diabetic to remain obese is to make more probable the early development of degenerative complications and to encourage an unfavorable influence on his longevity. Furthermore, to give insulin to obese patients, who are relatively resistant to it, is a wasteful practice. An obese diabetic may require 30 to 100 units of insulin to accomplish no more than can be attained by a highly desirable reduction in weight by reducing the total caloric intake. Insulin should be given to all child diabetics, to all thin adult diabetics whose diabetes is not under perfect control on a diet liberal enough to correct the malnourished state, to all pregnant diabetics, and to all diabetics, obese or thin, who during acute complications exhibit hyperglycemia and glycosuria. 2. Plans of insulin therapy for the patient with no acute complications are given in Table 1. A small percentage, possibly 10 per cent, of patients needing insulin will achieve good control of the diabetes with a single dose of an intermediate acting insulin-globin, NPH or Lente. For practical purposes the effects of these three insulins are identical. This single dose is given, preferably, an hour before breakfast. Its favorable effect
Treatment for Diabetes and Its Acute Complications
1581
is enhanced if a bread and milk exchange is taken from the breakfast to be consumed between 4 and 4:30 P.M. A somewhat larger percentage of patients need, if a forenoon hyperglycemia of undue degree is to be avoided, a rapidly acting insulin, as well as an insulin with an intermediate effect, before breakfast. This is achieved by adding some regular insulin to NPH insulin and giving it one-fourth hour before breakfast. This mixture, illustrated in Table 1, gives a much more predictable result than if regular insulin is added to globin or to Lente insulin. Table 1 ILLUSTRATIVE SIMPLE AND EFFECTIVE SCHEMES OF INSULIN THERAPY IN THE ABSENCE OF ACUTE COMPLICATIONS
I.
Mild Diabetes-Obese Patients
No insulin.
n.
Relatively Mild Diabetes
One dose of an intermediate insulin 1 hour before breakfast; e.g., 14 units of globin (or NPH or Lente) insulin.
Ill. Moderately Severe but Relatively Stable Diabetes A mixture of NPH and regular insulin X hour before breakfast, e.g., 12 units of regular insulin to which are added 40 units of PNH insulin.
IV. Severe and Labile Diabetes A mixture of NPH and regular insulin X hour before breakfast and a small dose of an intermediate insulin after supper; e.g., 16 units of regular insulin added to 60 units of NPH insulin X hour before breakfast and 10 units NPH (or globin or Lente) insulin after supper.
For a still larger percentage of patients comprising the young diabetics and the patients with labile or moderately severe and severe diabetes, the most effective plan, in my experience, is to give a mixture of NPH and regular insulins one-fourth hour before breakfast and a small dose of NPH insulin after supper. The evening dose may in some cases be given at bedtime. The diet with this program is divided into three equal meals, but a bread and milk exchange is taken from breakfast for consumption at 4:00 P.M. and a similar amount is taken from supper for consumption at bedtime. These three simple plans of insulin therapy have proved most effective, though other plans may suffice equally well in individual patients. ACUTE COMPLICATIONS
Three plans, some of which may suffice in all acute complications, barring ketosis, are recommended. First, for mild infections and the physical inactivity that may accompany them, small increases in the
1532
Garfield G. Duncan
insulin dosage are made without changing the pattern of administration. Second, for moderately severe infections, the usual basic dosage of insulin is maintained undisturbed, but regular insulin is given every four hours while the acute complications persist. The dosage is steadily increased to control glycosuria and it is quickly reduced as the complication subsides. Third, for the severe acute complication for which hospitalization is necessary, examples being a carbuncle, pneumonia or myocardial infarction, the diet is divided into four equal meals which are consumed at equally spaced intervals-every six hours, around the clock. Regular insulin only is used and it is given before each nourishment, the amounts being increased as necessary to achieve reasonably good control of the glycosuria and rapidly decreased as the acute complication subsides. This plan, using only one insulin for severe acute complications, gives a much more uniform effect and avoids the confusion which must result if an intermediate or long-acting insulin is added to the program. This simple plan of dealing with severe acute complications has met with widespread adoption, which is good evidence of its effectiveness. KETONEMIA-DIAGNOSIS OF DIABETIC COMA
A positive diagnosis of diabetic coma can be made in a matter of minutes. First, the urine is tested for sugar. All patients in diabetic coma will have grade 4 plus glycosuria. Second, a sample of blood, approximately 10 cc., is taken and placed in a test tube with sufficient potassium oxalate to prevent clotting. This is allowed to stand until a drop of clear plasma can be drawn off the surface* and placed on an Acetest tablet. t If the resulting color indicates a 4 plus reaction for ketones, the diagnosis of diabetic coma is established. No other condition is known that causes both 4 plus glycosuria and 4 plus ketonemia. An early diagnosis made in the home permits the immediate administration of 100 units of regular insulin to the adult patient-one-quarter of this amount may be given to the diabetic child-and 8 ounces of salty broth orally. This is usually well tolerated when the diagnosis is made early. With treatment under way, the patient is transferred to the hospital. On the patient's admission to the hospital the degree of ketonemia is studied further while other laboratory studies are under way. A portion of the plasma which gives a grade 4 reaction for ketones is diluted 1: 1 .with water or saline and this diluted specimen is tested for the degree of ketonemia. If a grade 4 plus reaction results, a further dilution of 1: 1 is made, and if this second dilution gives a grade 4 plus reaction, the patient is in profound coma and an additional 200 units of regular insulin
* Guest has recommended a more rapid method of securing plasma. He uses a dropper or pipette with cotton twisted about the tip. The cotton covered tip is lowered into the specimen of blood and the sample to be tested is drawn through the cotton. The pipette is withdrawn, the cotton is removed, and a drop of plasma is expressed on the reagent. t Manufactured by Ames Co. of Elkart, Indiana.
Treatment for Diabetes and Its Acute Complications
1583
are given (to the adult) followed by 50 units every half hour until an appreciable decrease in the degree of ketosis is noted. As the degree of ketosis subsides, the sensitivity to insulin returns. It is for this reason that we test for plasma ketones at two hour intervals. As soon as the undiluted plasma gives a reaction of less degree than grade 4 plus ketonemia, the amounts of insulin are 8harply reduced and at least four hours are allowed to elapse between d08cs. With a clearing of the ketonemia, barring the pre8ence of other acute complications, the patient's normal regimen is restored with 8uitable adjustments in the dosage of insulin being made to secure control of the diabetes. It is often preferable to allow four equal nourishments-one every six hours-for 24 hours after recovery from coma with a dose of regular insulin before each. Other studies are made. These are incorporated in the outline of therapy for diabetic coma (see below). The level of the blood sugar during the first six hours of therapy is not considered nearly as reliable a guide in the administration of insulin as is the degree of ketonemia. The value of knowing the lev,el of the blood sugar is the a8surance that it is not too low. The level of the blood sugar is checked at four hour intervals, chiefly to be sure it is kept well above normal until the ketosis is alleviated. Should the value drop below 250 mg. per 100 cc., intravenous administration of glucose is started to avoid the liJossibility of a hypoglycemia to which these patients are extremely susceptible when the ketosis has subsided, but before glycogen reserves have been appreciably replenished. If a patient regains consciousness and is doing well for several hours and then becomes unconscious again, an immediate recheck for plasma ketones will indicate their absence if a hypoglycemia is the offender. In such cases, the tragic mistake of giving more insulin in the belief that the patient has slipped back into diabetic coma is not infrequent. The simple test for ketonemia is of inestimable value if there is doubt. If the essentials for doing this test are not at hand, it is recommended that after a specimen of blood is taken for analysis-sugar and CO2 combining power-glucose be given intravenously immediately. This will not harm the ketotic patient and it will quickly restore consciousness to the hypoglycemic individual. In conclusion, the values of highly practical and simple measures which aid in the diagnosis and treatment of both complicated and uncomplicated diabetes have been stressed. In order that the application of the recommended plans for the treatment of diabetic coma may be interpreted in the light of more complete and parallel studies, the Guide to the Treatment of Diabetic Coma as employed at the Pennsylvania Hospital is presented. GUIDE TO THE TREATMENT OF DIABETIC COMA The working diagnosis of diabetic coma is made when a 4- plus reaction for glycosuria and 4- plus reaction for plasma ketones are found in an acutely ill patient. When these findings are~present:
Garfield G. Duncan
1584 I. Treatment is begun immediately:
INSULIN (regular) 100 units; if a 4+ reaction for ketonemia occurs only in the undiluted plasma; if a 4+ reaction for ketonemia is found in a 1:1 dilution of plasma with saline the initial dose is 200 units, but if a 4+ reaction is also present in the second dilution the initial dose is 300 units of insulin. Approximately onethird of the initial dose is given intravenously and two-thirds subcutaneously. * For children under 12 the initial dosage is approximately one-quarter of the dose for adults. FLUIDS AND CHLORIDES-2000 cc. normal saline are given to the adult patient (give rapidly 15 to 20 cc. per minute). Il. Studies. Secure immediately: (1) Blood for sugar content, ketones, hematocrit, CO 2 combining power, specific gravity (whole blood), and urea determinations. (2) Urine for culture and routine complete analysis. (3) Search for infection. Table 2 DIABETIC COMA-STUDIES AND THERAPY RECORD, PENNSYLVANIA HOSPITAL
__Day___ Half Day of Treatment ___Time Hours of Treatment Studies: Blood sugar ketones CO 2
hematocrit spec. grav. urea nitrogen potassiumt Urine sugar ketone culture analysis EKG Blood pressure
0
1
* * * * *
2
* *
4
* * * * * *
*
"
>;.
* *
"
3
_ _ _ _ _Name___U. H. No.
*
*
*
5
6
7
8
9
10
11
12
*
* *
*
* *
*
* *
* *
* * *
* * * *
*
"
* * *
*
*
*
*
*
*
* Indicates intervals at which the respective studies are usually performed. t In severe cases of ketosis. Ill. The Director of the Medical Division, or failing to reach him, a senior assistant will be notified promptly by the resident of the admission of a patient in diabetic coma. The resident will also alert the laboratory for emergency studies. IV. Secure urine at 2 hour intervalst for sugar determinations until the ketosis is corrected.
* With the exception of the initial dose and when patient is in shocklike state, all insulin is administered subcutaneously. t A retention catheter may be used for this purpose when necessary. Utmost care is taken to avoid introducing infection. As prophylactic measures, erythromycin 250 mg. is given parenterally at 6 hour intervals and as soon as is practicable Gantrisin 0.5 gram is given orally at 4 hour intervals until catheter has been removed.
Treatmentjor Diabetes and Its Acute Complications
v.
1585
Secure blood specimens at 2 hour intervals, day and night, for ketones and a 4 hour intervals for CO 2 and sugar, hematocrit reading, and specific gravity (whole blood) until the patient is conscious and retaining nourishment by mouth. Subsequent studies as conditions indicate.
VI. Secure an electrocardiogram as early as is practicable and repeat at 4 hour intervals until oral feedings have been retained for 4 hours. More frequent tracings and blood potassium determinations are indicated to guide therapy in cases of hypopotassemia. VII. Treatment During Critical Phase Subsequent to the Preliminary Measures Outlined in I
(a) Severe degree of ketosis with 4+ reaction for plasma ketones in the first and second dilutions: Insulin (regular) 50 units subcutaneously at one-half hour intervals until an appreciable reduction of the plasma ketones, or increase in the CO2 combining power, is noted. Increases above these amounts will rarely be necessary, but if no apparent decrease in the plasma ketones or increase in CO 2 combining power of the blood plasma has occurred after 6 hours* of therapy, each succeeding dose may be increased by 25 units until such changes are noted. (b) Mild degrees of ketosis (with 4+ reaction for plasma ketones in undiluted plasma only) : Insulin (regular) 50 units at 3 hour intervals until an appreciable reduction in ketonemia occurs. Dangers of a rapidly developing hypoglycemia will be avoided by giving 1 liter of glucose (5 per cent solution) or fructose (10 per cent solution) intravenously after 6 hours of therapy (See Par. X), or carbohydrate orally if practicable.
VIII. When to Reduce Insulin An appreciable reduction of the plasma ketones and an appreciable increase of the CO2 combining power of the blood plasma coincide with a lessening of the resistance to insulin. Such findings should alert the physician to the possibility.of a rapidly developing hypoglycemia. When the clinical condition of laboratory findings indicate that the patient is showing satisfactory progress, the insulin dosage is scheduled on a 3 or 4 hour basis as follows: 4 plus glycosuria-30 units 3 plus glycosuria-reduce to 20 units 2 plus glycosuria-reduce to 10 units 1 plus glycosuria-omit dose o glycosuria-omit insulin until glycosuria returns and give 20 grams carbohydrate stat The reduction of plasma ketones to 2+ or less (undiluted plasma) or an increase of the CO2 combining power to a value above 35 volumes per cent is, if the clinical condition of the patient permits, indication for insulin and diet at 6 hour intervals. (See Par. XIII.)
• It is common to find little change in the blood findings in the first 4 hours, but by the end of 6 hours improvement should be noted unless unusual circumstances are . present.
1586
Garfield G. Duncan
IX. Fluids and Salts Loss "of electrolytes and fluid occurs to a marked degree in the development of diabetic coma. Correction of these deficiencies is begun at the earliest opportunity. This is done properly by the administration of physiological saline solution, in amounts of 2000 to aooo cc., within the first 4 hours of treatment. Further administration is given freely while the specific gravity of the whole blood remains above 1.055, while hematocrit values remain above 50 per cent and the systolic blood pressure remains below 90 mm. Hg. NOTE: Do not give more than 24 grllms of NaCl in the first 24 hours of therapy. When necessary use fructose or glucose to achieve relative isotonicity. As soon as the patient's condition permits, broths, and later carbohydrate-containing fluids-strained cereal, gruel, ginger ale (noneffervescent), sweetened tea and later fruit juices-may be given. Potassium chloride, 1 gram every 4 hours for five doses, is given, as routine, after 6 hours of therapy, to the adult patient, provided urine is being excreted freely. Relatively smaller amounts are given to children. Accurate records of fluid intake and output are essential. X. Carbohydrate
Glucose or fructose, 1000 cc. of a 5 per cent solution in normal saline, is given intravenously bel!;inning 6 hours after the first dose of insulin is given, if at this time liquids given orally are not retained. Repeat in 6 hours if the patient is not taking or retaining nourishment by mouth.
XI. Alkali The administration of alkali usually is not necessary. However, an amount of racemic sodium lactate sufficient to raise the CO 2 combining power to a relatively innocent level-30 volumes per cent~-will relieve air hunger rapidly. Larger amounts are contraindicated. The foregoing amount of alkali is permissible, also, for the critically ill patient having a plasma CO 2 combining power below 15 volumes per cent. A transfusion using whole blood is an efficient means of restoring both base and blood volume, but is rarely necessary.
XIL Gastric Lavage-Enema The stomach is emptied and in cases of abdominal distention, abdominal pain or persistent vomiting, 8 ounces of warm normal saline solution-containing thorazine 25 mg. if an antiemetic is indicated-are left in the stomach. An enema is indicated in nearly every case of coma. It may be delayed until appreciable improvement in the patient's cDndition is noted.
XIII. Diet The diet, for 24 hours after the ketosis has subsided, will be divided into four equal nourishments~-one every 6 hours-and each will be preceded by a dose of regular insulin. Subsequently, barring acute complications, the patient's normal regimen with suitable adjustments in the insulin dosage is resumed. 330 S. 9th Street Philadelphia 7, Pennsylvania
THE therapy for diabetes is not simple, but too often medical writings on this subject make it more complex than it need be in the light of present day knowledge. Too often details of study and therapy have been kept on the research level instead of being reduced to those essentials necessary for clinical application. It is my purpose to deal with plans of management of the diabetic patient which lend themselves to the most practical application and which are shorn of needless complexity, with the hope that they will be widely and effectively adopted. These plans deal with:
A. Detection of diabetes-a simplified means of identifying diabetes in doubtful cases B. Insulin therapy 1. Which patients do and which patients do not need to be given insulin 2. Plans of insulin therapy in the absence of acute complications C. The management of diabetes during acute complications D. Tests for ketonemia 1. A most reliable but little used test for the detection of diabetic coma at the bedside-a simple test for the degree of ketonemia. The value of this test is just beginning to receive the attention it deserves. 2. The degree of ketonemia as a guide in the treatment for diabetic coma DETECTION OF DIABETES
The diagnosis of diabetes is a simple matter when the classical symptoms, glycosuria and hyperglycemia, are present, in which case no further diagnostic studies are necessary. In individuals who exhibit none of these manifestations, but in whom diabetes may be suspected, a specimen of blood taken two hours after a liberal meal may have a sugar content above 170 mg. per 100 cc., and if so it usually indicates diabetes. Fasting blood sugar values are often normal in the presence of mild diabetes, hence the value of a postprandial test. ,.. Clinical Professor of Medicine, JejJerson Medical College; Director of the Medical Division8 of the Pennsylvania Hospital and the Benjamin Franklin Clinic. 1579
Garfield G. Duncan
1580
Glucose tolerance tests are indicated when the diabetes cannot be detected or ruled out without them. A simplified glucose tolerance test, which is mentioned in another paper in this symposium and which we have used as a screening test for six years at the Benjamin Franklin Clinic, comprises (a) the giving of 100 grams of glucose in a pint of water flavored with lemon and (b) taking a single specimen of venous blood two hours after the glucose is given. If the blood sugar value (Folin-Wu method) is below 120 mg. per 100 cc., one can safely conclude that there is no detectable evidence of diabetes. If the value exceeds 140 mg., the diagnosis of diabetes is indicated provided suitable precautions outlined by Parkhurst and Betsch (see p. 1572) are taken. Values between 120 and 140 mg. are inconclusive and the test should be repeated several weeks later. This simple diagnostic procedure is not so cumbersome as the usual glucose tolerance test, and I do not believe its simplicity sacrifices in the slightest its diagnostic value. Its simplicity should encourage widespread adoption, particularly in the screening of possible candidates for diabetes, notably overweight relatives of diabetic patients. INSULIN THERAPY
1. Which patients should be given and which should not be given insulin? The obese diabetic free from acute complications does not need insulin therapy. The diabetes is mild and usually will be controlled within two or three weeks if a reducing diet is adhered to. If insulin is given to these patients, they will attribute the control of the diabetes to the insulin and consider the diet to be of secondary importance. The result is that they rarely reduce weight appreciably and continue on insulin therapy indefinitely. To permit a diabetic to remain obese is to make more probable the early development of degenerative complications and to encourage an unfavorable influence on his longevity. Furthermore, to give insulin to obese patients, who are relatively resistant to it, is a wasteful practice. An obese diabetic may require 30 to 100 units of insulin to accomplish no more than can be attained by a highly desirable reduction in weight by reducing the total caloric intake. Insulin should be given to all child diabetics, to all thin adult diabetics whose diabetes is not under perfect control on a diet liberal enough to correct the malnourished state, to all pregnant diabetics, and to all diabetics, obese or thin, who during acute complications exhibit hyperglycemia and glycosuria. 2. Plans of insulin therapy for the patient with no acute complications are given in Table 1. A small percentage, possibly 10 per cent, of patients needing insulin will achieve good control of the diabetes with a single dose of an intermediate acting insulin-globin, NPH or Lente. For practical purposes the effects of these three insulins are identical. This single dose is given, preferably, an hour before breakfast. Its favorable effect
Treatment for Diabetes and Its Acute Complications
1581
is enhanced if a bread and milk exchange is taken from the breakfast to be consumed between 4 and 4:30 P.M. A somewhat larger percentage of patients need, if a forenoon hyperglycemia of undue degree is to be avoided, a rapidly acting insulin, as well as an insulin with an intermediate effect, before breakfast. This is achieved by adding some regular insulin to NPH insulin and giving it one-fourth hour before breakfast. This mixture, illustrated in Table 1, gives a much more predictable result than if regular insulin is added to globin or to Lente insulin. Table 1 ILLUSTRATIVE SIMPLE AND EFFECTIVE SCHEMES OF INSULIN THERAPY IN THE ABSENCE OF ACUTE COMPLICATIONS
I.
Mild Diabetes-Obese Patients
No insulin.
n.
Relatively Mild Diabetes
One dose of an intermediate insulin 1 hour before breakfast; e.g., 14 units of globin (or NPH or Lente) insulin.
Ill. Moderately Severe but Relatively Stable Diabetes A mixture of NPH and regular insulin X hour before breakfast, e.g., 12 units of regular insulin to which are added 40 units of PNH insulin.
IV. Severe and Labile Diabetes A mixture of NPH and regular insulin X hour before breakfast and a small dose of an intermediate insulin after supper; e.g., 16 units of regular insulin added to 60 units of NPH insulin X hour before breakfast and 10 units NPH (or globin or Lente) insulin after supper.
For a still larger percentage of patients comprising the young diabetics and the patients with labile or moderately severe and severe diabetes, the most effective plan, in my experience, is to give a mixture of NPH and regular insulins one-fourth hour before breakfast and a small dose of NPH insulin after supper. The evening dose may in some cases be given at bedtime. The diet with this program is divided into three equal meals, but a bread and milk exchange is taken from breakfast for consumption at 4:00 P.M. and a similar amount is taken from supper for consumption at bedtime. These three simple plans of insulin therapy have proved most effective, though other plans may suffice equally well in individual patients. ACUTE COMPLICATIONS
Three plans, some of which may suffice in all acute complications, barring ketosis, are recommended. First, for mild infections and the physical inactivity that may accompany them, small increases in the
1532
Garfield G. Duncan
insulin dosage are made without changing the pattern of administration. Second, for moderately severe infections, the usual basic dosage of insulin is maintained undisturbed, but regular insulin is given every four hours while the acute complications persist. The dosage is steadily increased to control glycosuria and it is quickly reduced as the complication subsides. Third, for the severe acute complication for which hospitalization is necessary, examples being a carbuncle, pneumonia or myocardial infarction, the diet is divided into four equal meals which are consumed at equally spaced intervals-every six hours, around the clock. Regular insulin only is used and it is given before each nourishment, the amounts being increased as necessary to achieve reasonably good control of the glycosuria and rapidly decreased as the acute complication subsides. This plan, using only one insulin for severe acute complications, gives a much more uniform effect and avoids the confusion which must result if an intermediate or long-acting insulin is added to the program. This simple plan of dealing with severe acute complications has met with widespread adoption, which is good evidence of its effectiveness. KETONEMIA-DIAGNOSIS OF DIABETIC COMA
A positive diagnosis of diabetic coma can be made in a matter of minutes. First, the urine is tested for sugar. All patients in diabetic coma will have grade 4 plus glycosuria. Second, a sample of blood, approximately 10 cc., is taken and placed in a test tube with sufficient potassium oxalate to prevent clotting. This is allowed to stand until a drop of clear plasma can be drawn off the surface* and placed on an Acetest tablet. t If the resulting color indicates a 4 plus reaction for ketones, the diagnosis of diabetic coma is established. No other condition is known that causes both 4 plus glycosuria and 4 plus ketonemia. An early diagnosis made in the home permits the immediate administration of 100 units of regular insulin to the adult patient-one-quarter of this amount may be given to the diabetic child-and 8 ounces of salty broth orally. This is usually well tolerated when the diagnosis is made early. With treatment under way, the patient is transferred to the hospital. On the patient's admission to the hospital the degree of ketonemia is studied further while other laboratory studies are under way. A portion of the plasma which gives a grade 4 reaction for ketones is diluted 1: 1 .with water or saline and this diluted specimen is tested for the degree of ketonemia. If a grade 4 plus reaction results, a further dilution of 1: 1 is made, and if this second dilution gives a grade 4 plus reaction, the patient is in profound coma and an additional 200 units of regular insulin
* Guest has recommended a more rapid method of securing plasma. He uses a dropper or pipette with cotton twisted about the tip. The cotton covered tip is lowered into the specimen of blood and the sample to be tested is drawn through the cotton. The pipette is withdrawn, the cotton is removed, and a drop of plasma is expressed on the reagent. t Manufactured by Ames Co. of Elkart, Indiana.
Treatment for Diabetes and Its Acute Complications
1583
are given (to the adult) followed by 50 units every half hour until an appreciable decrease in the degree of ketosis is noted. As the degree of ketosis subsides, the sensitivity to insulin returns. It is for this reason that we test for plasma ketones at two hour intervals. As soon as the undiluted plasma gives a reaction of less degree than grade 4 plus ketonemia, the amounts of insulin are 8harply reduced and at least four hours are allowed to elapse between d08cs. With a clearing of the ketonemia, barring the pre8ence of other acute complications, the patient's normal regimen is restored with 8uitable adjustments in the dosage of insulin being made to secure control of the diabetes. It is often preferable to allow four equal nourishments-one every six hours-for 24 hours after recovery from coma with a dose of regular insulin before each. Other studies are made. These are incorporated in the outline of therapy for diabetic coma (see below). The level of the blood sugar during the first six hours of therapy is not considered nearly as reliable a guide in the administration of insulin as is the degree of ketonemia. The value of knowing the lev,el of the blood sugar is the a8surance that it is not too low. The level of the blood sugar is checked at four hour intervals, chiefly to be sure it is kept well above normal until the ketosis is alleviated. Should the value drop below 250 mg. per 100 cc., intravenous administration of glucose is started to avoid the liJossibility of a hypoglycemia to which these patients are extremely susceptible when the ketosis has subsided, but before glycogen reserves have been appreciably replenished. If a patient regains consciousness and is doing well for several hours and then becomes unconscious again, an immediate recheck for plasma ketones will indicate their absence if a hypoglycemia is the offender. In such cases, the tragic mistake of giving more insulin in the belief that the patient has slipped back into diabetic coma is not infrequent. The simple test for ketonemia is of inestimable value if there is doubt. If the essentials for doing this test are not at hand, it is recommended that after a specimen of blood is taken for analysis-sugar and CO2 combining power-glucose be given intravenously immediately. This will not harm the ketotic patient and it will quickly restore consciousness to the hypoglycemic individual. In conclusion, the values of highly practical and simple measures which aid in the diagnosis and treatment of both complicated and uncomplicated diabetes have been stressed. In order that the application of the recommended plans for the treatment of diabetic coma may be interpreted in the light of more complete and parallel studies, the Guide to the Treatment of Diabetic Coma as employed at the Pennsylvania Hospital is presented. GUIDE TO THE TREATMENT OF DIABETIC COMA The working diagnosis of diabetic coma is made when a 4- plus reaction for glycosuria and 4- plus reaction for plasma ketones are found in an acutely ill patient. When these findings are~present:
Garfield G. Duncan
1584 I. Treatment is begun immediately:
INSULIN (regular) 100 units; if a 4+ reaction for ketonemia occurs only in the undiluted plasma; if a 4+ reaction for ketonemia is found in a 1:1 dilution of plasma with saline the initial dose is 200 units, but if a 4+ reaction is also present in the second dilution the initial dose is 300 units of insulin. Approximately onethird of the initial dose is given intravenously and two-thirds subcutaneously. * For children under 12 the initial dosage is approximately one-quarter of the dose for adults. FLUIDS AND CHLORIDES-2000 cc. normal saline are given to the adult patient (give rapidly 15 to 20 cc. per minute). Il. Studies. Secure immediately: (1) Blood for sugar content, ketones, hematocrit, CO 2 combining power, specific gravity (whole blood), and urea determinations. (2) Urine for culture and routine complete analysis. (3) Search for infection. Table 2 DIABETIC COMA-STUDIES AND THERAPY RECORD, PENNSYLVANIA HOSPITAL
__Day___ Half Day of Treatment ___Time Hours of Treatment Studies: Blood sugar ketones CO 2
hematocrit spec. grav. urea nitrogen potassiumt Urine sugar ketone culture analysis EKG Blood pressure
0
1
* * * * *
2
* *
4
* * * * * *
*
"
>;.
* *
"
3
_ _ _ _ _Name___U. H. No.
*
*
*
5
6
7
8
9
10
11
12
*
* *
*
* *
*
* *
* *
* * *
* * * *
*
"
* * *
*
*
*
*
*
*
* Indicates intervals at which the respective studies are usually performed. t In severe cases of ketosis. Ill. The Director of the Medical Division, or failing to reach him, a senior assistant will be notified promptly by the resident of the admission of a patient in diabetic coma. The resident will also alert the laboratory for emergency studies. IV. Secure urine at 2 hour intervalst for sugar determinations until the ketosis is corrected.
* With the exception of the initial dose and when patient is in shocklike state, all insulin is administered subcutaneously. t A retention catheter may be used for this purpose when necessary. Utmost care is taken to avoid introducing infection. As prophylactic measures, erythromycin 250 mg. is given parenterally at 6 hour intervals and as soon as is practicable Gantrisin 0.5 gram is given orally at 4 hour intervals until catheter has been removed.
Treatmentjor Diabetes and Its Acute Complications
v.
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Secure blood specimens at 2 hour intervals, day and night, for ketones and a 4 hour intervals for CO 2 and sugar, hematocrit reading, and specific gravity (whole blood) until the patient is conscious and retaining nourishment by mouth. Subsequent studies as conditions indicate.
VI. Secure an electrocardiogram as early as is practicable and repeat at 4 hour intervals until oral feedings have been retained for 4 hours. More frequent tracings and blood potassium determinations are indicated to guide therapy in cases of hypopotassemia. VII. Treatment During Critical Phase Subsequent to the Preliminary Measures Outlined in I
(a) Severe degree of ketosis with 4+ reaction for plasma ketones in the first and second dilutions: Insulin (regular) 50 units subcutaneously at one-half hour intervals until an appreciable reduction of the plasma ketones, or increase in the CO2 combining power, is noted. Increases above these amounts will rarely be necessary, but if no apparent decrease in the plasma ketones or increase in CO 2 combining power of the blood plasma has occurred after 6 hours* of therapy, each succeeding dose may be increased by 25 units until such changes are noted. (b) Mild degrees of ketosis (with 4+ reaction for plasma ketones in undiluted plasma only) : Insulin (regular) 50 units at 3 hour intervals until an appreciable reduction in ketonemia occurs. Dangers of a rapidly developing hypoglycemia will be avoided by giving 1 liter of glucose (5 per cent solution) or fructose (10 per cent solution) intravenously after 6 hours of therapy (See Par. X), or carbohydrate orally if practicable.
VIII. When to Reduce Insulin An appreciable reduction of the plasma ketones and an appreciable increase of the CO2 combining power of the blood plasma coincide with a lessening of the resistance to insulin. Such findings should alert the physician to the possibility.of a rapidly developing hypoglycemia. When the clinical condition of laboratory findings indicate that the patient is showing satisfactory progress, the insulin dosage is scheduled on a 3 or 4 hour basis as follows: 4 plus glycosuria-30 units 3 plus glycosuria-reduce to 20 units 2 plus glycosuria-reduce to 10 units 1 plus glycosuria-omit dose o glycosuria-omit insulin until glycosuria returns and give 20 grams carbohydrate stat The reduction of plasma ketones to 2+ or less (undiluted plasma) or an increase of the CO2 combining power to a value above 35 volumes per cent is, if the clinical condition of the patient permits, indication for insulin and diet at 6 hour intervals. (See Par. XIII.)
• It is common to find little change in the blood findings in the first 4 hours, but by the end of 6 hours improvement should be noted unless unusual circumstances are . present.
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Garfield G. Duncan
IX. Fluids and Salts Loss "of electrolytes and fluid occurs to a marked degree in the development of diabetic coma. Correction of these deficiencies is begun at the earliest opportunity. This is done properly by the administration of physiological saline solution, in amounts of 2000 to aooo cc., within the first 4 hours of treatment. Further administration is given freely while the specific gravity of the whole blood remains above 1.055, while hematocrit values remain above 50 per cent and the systolic blood pressure remains below 90 mm. Hg. NOTE: Do not give more than 24 grllms of NaCl in the first 24 hours of therapy. When necessary use fructose or glucose to achieve relative isotonicity. As soon as the patient's condition permits, broths, and later carbohydrate-containing fluids-strained cereal, gruel, ginger ale (noneffervescent), sweetened tea and later fruit juices-may be given. Potassium chloride, 1 gram every 4 hours for five doses, is given, as routine, after 6 hours of therapy, to the adult patient, provided urine is being excreted freely. Relatively smaller amounts are given to children. Accurate records of fluid intake and output are essential. X. Carbohydrate
Glucose or fructose, 1000 cc. of a 5 per cent solution in normal saline, is given intravenously bel!;inning 6 hours after the first dose of insulin is given, if at this time liquids given orally are not retained. Repeat in 6 hours if the patient is not taking or retaining nourishment by mouth.
XI. Alkali The administration of alkali usually is not necessary. However, an amount of racemic sodium lactate sufficient to raise the CO 2 combining power to a relatively innocent level-30 volumes per cent~-will relieve air hunger rapidly. Larger amounts are contraindicated. The foregoing amount of alkali is permissible, also, for the critically ill patient having a plasma CO 2 combining power below 15 volumes per cent. A transfusion using whole blood is an efficient means of restoring both base and blood volume, but is rarely necessary.
XIL Gastric Lavage-Enema The stomach is emptied and in cases of abdominal distention, abdominal pain or persistent vomiting, 8 ounces of warm normal saline solution-containing thorazine 25 mg. if an antiemetic is indicated-are left in the stomach. An enema is indicated in nearly every case of coma. It may be delayed until appreciable improvement in the patient's cDndition is noted.
XIII. Diet The diet, for 24 hours after the ketosis has subsided, will be divided into four equal nourishments~-one every 6 hours-and each will be preceded by a dose of regular insulin. Subsequently, barring acute complications, the patient's normal regimen with suitable adjustments in the insulin dosage is resumed. 330 S. 9th Street Philadelphia 7, Pennsylvania