Clinical features of hyperosmolar hyperglycemic nonketotic diabetic coma associated with cardiac operations

J

THoRAc CARDIOVASC SURG

91:867-873, 1986

Clinical features of hyperosmolar hyperglycemic nonketotic diabetic coma associated with cardiac operations Hyperosmolar hyperglycemic nonketotic diabetic coma after cardiac operations was reviewed in a total of 12 patients from the literature and from my experience in an attempt to determine the clinical features of this condition. Among the unique features of this disease were the following: (1) The mortality is high (42 %~ (2)The morbidity and mortality are higher in patients with no previous history of diabetes mellitus (67% and 50%) than in those with such a history (33% and 25%). (3) Polyuria is usually a heralding symptom. (4) There is an average time lag of 6 days between the onset of polyuria and the established diagnosis of hyperosmolar hyperglycemic nonketotic diabetic coma. (5) The time lag in patients who died was 7.5 ± 0.8 days (mean ± standard error of the mean), significantly longer than in survivors (4.5 ± 0.8 days). (6) Polyuria usually emerges after the stormy immediate postoperative days have passed (on postoperative day 5.3 on the average). (7) Polyuria is generally regarded as a favorable sign not suggestive of complicating hyperosmolar hyperglycemic nonketotic diabetic coma. (8) Therapies known to precipitate this disorder are continued even after development of polyuria. (9) Gastrointestinal bleeding can be a precipitating factor. (10) Hyperalimentation or elemental diet may cause dehydration and trigger hyperosmolar hyperglycemic nonketotic diabetic coma. (11) A high or rising serum sodium concentration and/or blood urea nitrogen level with polyuria may be a warning sign of this complication. (12) Too hasty correction of the hyperosmolar state can be dangerous. (13) Pulmonary dysfunction may be involved in the symptoms of hyperosmolar hyperglycemic nonketotic diabetic coma.

Shuji Seki, M.D., Okayama, Japan

Articles dealing with hyperosmolar hyperglycemic nonketotic diabetic coma associated with cardiac operations are, to my knowledge, very limited in number. In 1971 Mills, Isom, and Spencer' mentioned two cases, in 1972 Evans, Littler, and Meade- reported one case, and in 1973 Brenner and associates) cited three cases. Since then no article dealing with this disease has appeared in the English literature. In Japan three cases have been reported in the literature'" and I have encountered five. All articles published so far are individual reports and no collective review has ever been attempted. I conducted this study with the intention of determinFrom the Department of Acute Medicine, Okayama University School of Medicine, Okayama University, Okayama, Japan. Received for publication June II, 1985. Accepted for publication Aug. 6, 1985. Address for reprints: Shuji Seki, M.D., Acute Medicine, Okayama University School of Medicine, 2-5-1 Shikata, Okayama, Japan,

700.

ing unique features, if any, of hyperosmolar hyperglycemic nonketotic diabetic coma associated with cardiac operations by reviewing seven cases reported by others and five of my own. I hope this collective review may call the attention of cardiac surgeons to the importance of this condition in association with cardiac operations. The incidence of this complication must be much greater than that described in the literature and must be increasing with the increasing availability of more potent therapeutic modalities. Results Data on seven of the nine patients described in the literature plus my own five patients are listed in Table I. Patients 1 to 4 are from the English literature.s 3 Patients 5 to 7 are from the Japanese literature.t" and Patients 8 to 12 are from my experience. No sex prevalence was present (male/female ratio 6:6). The age of the patients was 51.3 ± 2.5 years (mean ± standard error of the mean). 867

868

The Journal of Thoracic and Cardiovascular Surgery

Seki

Table I. Clinical features of hyperosmolar nonketotic hyperglycemic diabetic coma (HHNKDC) in 12 patients Pt. No.

Age/sex

DM

Diagnosis/procedure performed

Drugs given Date

I

Drugs

Other complications Date I

Complications

53/p

Neg.

MS/MVR

2

Dvhydantoin furosemide Cortisone

2

59/M3

Pos., type 2

IHD/CABG

Preop.

Tolbutamide

None

3

58/M3

Pos., type 2

IHD/CABG

7

None

4

65/M3

Neg.

IDH/CABG

5

34/F'

Neg.

MR, ASR/MVR, AVR

Furosemide Ethacrynic acid Mercuhydrin Mannitol Glucagon Prcdnisone Furosemide Prednisone Solu-Cortcf Dopamine

0-7 Prcop. 2 3-6 8, 10 O-U

Preop. 3

Grand mal seizures Pneumonia (RUL)

7

Upper GI bleeding

5

Hypoxemia

6 7

Bleeding gastric ulcer Gastrectomy

Norepinephrine Steroid Diuretics Transfusion Diuretics Dopamine TPN

6

42/M'

Neg.

MR/MVR

O-U

7

59jP'

Neg.

MS, AS/MVR

Preop. O-U

Diuretics Dopamine

8

4l/M

Neg.*

AS, MSR, TR/AVR, OMC, TAP

O-U 5

Furosemide Elemental diet

14

9

47/F

Neg.

Prosthesis dysfunction/ MVR

O-U

O-U

None

Bleeding gastric ulcer

10

50/F

Neg.

MS/MVR

0-3

Diuretics Steroid Alcviatin Elemental diet 50(fr, Dextrose 50% Dextrose

II

5l/M

Pos., type 2

IHD/CABG

0-4 0-5

Dopamine Diuretics

0-5

Hypoxemia (Pao,! F1o,:95-180)

12

57/F

Neg.

MS, AR/MVR

0-5 2-11 0-17

Dopamine

Elemental diet

1-4 11 12

Oliguria (hemodialysis on 4-6 POD) Bleeding gastric ulcer Plasmapheresis (for high S.Na)

8

Furosemide

Cerebral embolism

None

Legend: DM, Diabetes mellitus. Date, Postoperative day (unless preoperatively). Preop., Before cardiacoperation. Neg.. No history of diabetes mellitus. Pos., Positive history of diabetes mellitus. MS, Mitral stenosis. MYR, Mitral valve replacement. IHD, Ischemic heart disease. CAGB,Coronary artery bypass grafting. ASR, Aortic stenosis and regurgitation. AYR,Aorticvalve replacement. AS, Aortic stenosis. MSR, Mitralstenosis and regurgitation. TR, Tricuspid regurgitation. OMC,Open mitral commissurotomy. TAP, Tricuspid annuloplasty. U, Uncertain date of discontinuance. Diuretics. Diuretic(s) other than furosemide. with or without furosemide, was

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Hyperosmolar hyperglycemic nonketotic diabetic coma

June, 1986

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HHNKDC Date

Initial signs or data Polyuria (100 ml/hr) Drowsy Confused None

Diagnosis established 10

0

0

BG:600 mg/dl

8

2

Polyuria (50-100 rnl/hr) Lethargic Confused

8

II 13

Polyuria (100 rnl/hr) Confused

14

2 6

Polyuria (2,500 ml/day) Restlessness

8

2

Polyuria (200-300 rnl/hr) Lethargic BUN:35-50 mg/d! BS:4oo rng/dl S.Na:151 mEq/L BUN:60 rng/dl, CRTN: 2.75 Polyuria (3,600 ml/day) Lethargic

4

3

15

II 16

Polyuria (2,500 mljday) Semicoma

20

17

Polyuria (60 ml/hr) Restlessness

4

0 I

Polyuria (200 ml/hr) S.Na:149 mEq/L

2

9 II

Polyuria (3,900 ml/day) Lethargic Muscular twitching BG:3oo rng/dl (max:729 on 12 POD) S.Na:166 mfiq/L (max:173 on 12 POD) S.Osm:396 mOsm/L

12

4 14

Coma BG:744mg/dl, S.Osm:370mOsm/L S.Na:158 mliq/L BUN:30 mg/dl Semicoma BG:495 rng/dl (max.:645 mg/dl) S.Osm:323 rrrOsm/L BG:I,500 rng/dl S.Na:160 mEq/L (max.:187 mEq/L) BUN:126 mg/dl

BG:556 rng/dl BUN:350 rng/dl S.Na:164 mEq/1 S.Osm:498 mOsm/L (on 10 POD) Semicoma BG:I,037 rng/dl S.Osm:360 mOsm/L BUN:50 rng/dl Polyuria (200-300 ml/hr) BG:465 mg/dl S.Osm:360 mOsrn/L S.Na:158 mEq/L BUN:70 rng/dl BG:400 mg/dl S.Osm:403 nrOsrn/L

BG:592 rng/dl S.Osm:353 mOsm/L BUN:46 rng/dl Muscular twitching BG:310 mg/dl (max:684 on 19 POD) S.Na:134 mEq/L (max.S.Osm: 424 on 19 POD) BUN:169 rng/dl Coma BG: 1,400 rng/dl S.Osm:415 mOsm/L S.Na:146 mEq/L Pao,:55.4 torr (room air) BUN:83 mg/dl Thirst BG:236 rng/dl (max:338 on 3 POD) S.Osm:331 mOsm/L (max:382 on 4 POD) S.Na:148 mEq/L (max:155 on 3 POD) BUN:44 rng/dl Coma BG:308 rng/dl S.Osm:330 rnOsm/L S.Na:138 mEq/L BUN:58 mg/dl

Results Died

Survived

Died

Died

Survived

Survived

Survived

Survived

Died

Survived

Survived

Died

(were) administered. TPN, Total parenteral nutrition. RUL, Right upper lobe.GI, Gastrointestinal. BUN, Blood urea nitrogen.CRTN, Creatinine.S.Na, Serum sodium. BG, Blood glucose. S.Osm, Serum osmolality. POD, Postoperative day. ·Fasting bloodglucose level of 150 mgjdl.

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870 Seki

Patient No. 1+++++++++++++++++++++ 10 ( 10 )

1 4 5 6 7

2+++++++++++++++8(7) " 2-----------L

8(7)

4 (3)

8 9

~-----------m(6)

"++++++++++++++'7 (7) , +++++++++ 4 (4)

10

11

14 (4)

0

2 (3)

9+++++++++++14 (6)

12

53••••••••••• 10

Mean

1(5.7)

58++++++++++++'20

OD. day

(7.6) '"

8 i (4.5)"

l2

5

10

15

20

POD

Fig. 1. Time lag from onset of polyuria to establishment of diagnosis of hyperosmolar nonketotic hyperglycemic diabetic coma. +++, Patients who died. ---, Patients who survived. ***, Mean for all patients. Figures in parentheses, Days from onset of polyuria to diagnosis. @, Significant difference (p = 0.03). Numbers at the left and right ends of each bar indicate the postoperative day of the onset of polyuria and the establishment of the diagnosis, respectively.

Three patients (25%) were aware preoperatively of having diabetes mellitus, and preoperative laboratory study detected a high fasting blood glucose level in one. Thus one third were known to have diabetes preoperatively and two thirds were not. Polyuria was an initial sign of hyperosmolar hyperglycemic nonketotic diabetic coma in 10 patients (83.3%), but it did not direct the attending physicians to the correct diagnosis. Consequently there was a considerable delay before the diagnosis was established. The onset of polyuria ranged from the day of operation to the fifteenth postoperative day (5.3 ± 1.7), whereas the diagnosis was made from the second to the twentieth postoperative day (10.1 ± 1.8) (Fig. 1). Thus the time lag between development of the initial sign of polyuria and establishment of the diagnosis ranged from 3 to 10 days (5.7 ± 0.7 days). The delay in making the diagnosis after development of the initial sign was 7.5 ± 0.8 days (range 6 to 10 days) in patients who died and 4.5 ± 0.8 days (3 to 7 days) in survivors (significant, p = 0.03, by the unpaired Student's t test). Early or late onset of polyuria was not related to prognosis: a mean of 5.8 days postoperatively for patients who died and 5.2

for survivors. Sugar reaction of the urine was strongly positive and ketone bodies were negative in all the patients. Despite the presence of polyuria, diuretics were continued in nine patients and dopamine in one, which pushed the patients toward dehydration. Gastrointestinal bleeding occurred in four patients (33.3%) after the onset of polyuria but before the diagnosis of hyperosmolar hyperglycemic nonketotic diabetic coma. Two patients died. An elemental diet was used in three patients and total parenteral nutrition in one. In another patient a total of 320 gm of 50% dextrose was infused over 3 days. Thus five patients (41.7%) may have had a nutritional overload before and/or during the prodromal period of hyperosmolar hyperglycemic nonketotic diabetic coma. All but one patient (Patient 2) (91.6%) received medications that are known to precipitate this disorder, such as catecholamine, diuretics, glucagon, nutritional support, and steroid therapy before and/or during the prodromal period and even during the fullest extent of diabetic coma. Hypoxemia existed in two patients before the diagno-

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Hyperosmolar hyperglycemic nonketotic diabetic coma

sis was established. The attending physicians thought hypoxemia was due to pulmonary edema secondary to congestive heart failure that was evoked by the operation. However, the laboratory study could not explain it from a cardiac standpoint and the hypoxemia improved as the diabetic coma subsided. In both patients hypoxemia caused the attending physicians to initiate therapies leading toward dehydration because of the likely diagnosis of congestive heart failure. The serum sodium level was high (above 145 mEq/ L) in eight of nine patients (88.8%). In Patient 11 persistent hypematremia associated with polyuria was a clue to the diagnosis, and hyperosmolar hyperglycemic nonketotic diabetic coma was terminated before it reached its full extent. In Patient 12 severe hypematremia (173 mfiq/L) was corrected by plasmapheresis (2,400 ml), which lowered the sodium level to 152 mEq/L in 4 hours. Serum osmolality changed from 396 to 343 mOsm/L and the blood glucose level from 729 to 522 mg/dl. Consciousness, however, regressed from responsiveness to unresponsiveness, which suggests the danger of vigorously correcting the hyperosmolar state induced by hyperosmolar hyperglycemic nonketotic diabetic coma. The blood urea nitrogen (BUN) level, determined in 11 patients, also increased in all. BUN ranged from 30 to 350 mg/dl (123 ± 31 mg/dl). BUN levels in patients who died were 126 to 350 rng/dl (236 ± 46), except in Patient 12; she recovered from hyperosmolar hyperglycemic nonketotic diabetic coma but died of brain damage probably because of the vigorous correction of the hyperosmolar state. BUN levels in survivors were 44 to 83 mg/dl (59 ± 6 mg/dl), The difference in BUN between patients who survived and those who died is significant (p < 0.05). The blood glucose levels (the maximum value if determined more than once) ranged from 308 to 1,500 mg/dl (722 ± 109 mg/dl), Those of patients who died ranged from 308 to 1,500 mg/dl (758 ± 179 mg/dl) and those of the survivors, from 338 to 1,037 mg/dl (679 ± 135 mg/dl) (no significant difference). Serum osmolality, measured in all but one patient, ranged from 323 to 498 mOsm/L (383 ± 14 mOsm/L). The mean serum osmolality in the patients who died was 406 ± 32 mOsm/L, ranging from 330 to 498 mOsm/L, and that of the survivors was 371 ± 11, ranging from 323 to 415 mOsm/L (no statistically significant difference). The diagnosis of hyperosmolar hyperglycemic nonketotic diabetic coma was made earlier, although not significantly so, in the survivors than nonsurvivors: survivors, mean postoperative day 8.7 (range 2 to 20); nonsurvivors: postoperative day 12 (range 8 to 17). Overall mortality was 41.7% (5/12). One of the four

871

patients with diabetes mellitus or a high fasting blood glucose level died of hyperosmolar hyperglycemic nonketotic diabetic coma and four of the eight with neither diabetes mellitus nor a high fasting blood glucose level died of this complication. Thus the mortality of nondiabetic patients was twice as high as that of diabetic patients (50% versus 25%). Discussion In diabetic patients ketoacidosis ensues if excessive free fatty acids are mobilized from adipose tissue, and if free fatty acids are not mobilized, hyperosmolar hyperglycemic nonketotic diabetic coma develops. This difference results from the presence of very low plasma insulin concentrations." Very low insulin concentrations do not affect glucose uptake by cells yet still can inhibit release of free fatty acid from adipose tissue. Patients who are prone to hyperosmolar hyperglycemic nonketotic diabetic coma may do well except for transient hyperglycemia, which occurs when excessive load occurs in insulin consumption. With diabetogenic stress the pancreas eventually fatigues and the plasma insulin level falls to such an extent that hyperglycemia worsens but ketoacidosis is avoided. The diabetogenic stress of a cardiac operation, which includes surgical trauma, cardiopulmonary bypass, hypothermia, glucose overload, and excessive insulin adsorption by the cardiopulmonary bypass system, may be strong enough to induce fatigue of the pancreas. According to Gill, Sherif, and Alberti, IO the amount of insulin required to keep a constant blood glucose level during glucose loading is much greater in diabetic patients with cardiac disease (1.0 units/gm of glucose) than in those without cardiac disease (0.3 units/gm), Insulin requirements also increase postoperatively, being seven times greater during the first 4 hours than the preoperative requirement." Furthermore, diabetogenic stimuli such as catecholamines and diuretics are often used for postoperative management. I I, 12 Low cardiac output, hypovolemic shock, anticonvulsant agents, steroid therapy, and blood transfusion are also diabetogenic. I I, 13, 14 Parenteral nutrition, being used with increasing frequency, is also diabetogenic. IS, 16 With these multiple factors taken into account, patients undergoing cardiac operations are susceptible to hyperosmolar hyperglycemic nonketotic diabetic coma. No patients with hyperosmolar hyperglycemic nonketotic diabetic coma had a blood glucose level of less than 600 mg/dl," Podolsky" suggested that a blood glucose level greater than 600 mg/dl is a major clinical feature. Serum osmolality was usually above 350 mOsm/L,8,17 Lavine" suggested that an osmolality above 330 mOsm/L is consistent with hyperosmolar hyperglycemic nonketotic diabetic coma. According to these crite-

The Journal of

872 Seki

ria, all patients in this study had signs of this condition. However, it seems unreasonable to define this disease so rigidly, because these indices are applicable only to patients in whom hyperosmolar hyperglycemic nonketotic diabetic coma is at its fullest extent. A previous history of diabetes mellitus is less important in this condition than in other diabetic diseases. In this study four of 12 patients had a previous history of diabetes and the other two thirds did not. These percentages differ from the conventional concepts involving diabetes mellitus. Absence of a previous history does not always mean that hyperosmolar hyperglycemic nonketotic diabetic coma can be discounted but rather that surgeons should be more cautious of the disorder. After the initial symptom of polyuria appeared, a mean of 5.7 days elapsed before the diagnosis was established in survivors and 7.5 days in the patients who died. This time lag should be taken as evidence that cardiac surgeons are unawareness of hyperosmolar hyperglycemic nonketotic diabetic coma. This delay probably stemmed from their concept of polyuria. For cardiac surgeons an increase in urine output usually heralds an improvement in cardiac failure. In fact, cardiac failure occurs so often after heart operations that cardiac surgeons have become less cautious of polyuria than other surgeons. This concept of polyuria is evidenced by the fact that in this study diuretics were continuously given in all patients after polyuria occurred. Cardiac surgeons should consider the possibility of hyperosmolar hyperglycemic nonketotic diabetic coma when copious urinary volume is maintained with ease. Another pitfall to the recognition of this disorder is timing of its appearance. Polyuria started a mean of 5.3 days after the operation, at a time when, with the stormy immediate postoperative days just over, the attending physician's attention might unconsciously be lowered. Moreover, hyperosmolar hyperglycemic nonketotic diabetic coma progresses insidiously. Signs and symptoms other than polyuria are also indefinite. Gastrointestinal bleeding seems to precipitate hyperosmolar hyperglycemic nonketotic diabetic coma. The bleeding usually occurred when polyuria was under way. The consequent hypovolemic shock also produces a diabetes-like state." In shock the body stops its output of insulin. Energy substrates are mobilized to form new glucose, and thus output of glucose is increased. On the other hand, peripheral glucose uptake is inhibited by high cortisone and catecholamine levels, which results in marked hyperglycemia. However, the resultant hyper-

Thoracic and Cardiovascular Surgery

glycemia may be a self-defense mechanism." Blood glucose may be an important determinant of plasma refill on hypovolemic shock. The roles of hyperglycemia in hypovolemic shock may involve as their usage an osmotic agent and a substrate for energy metabolism. If this is the case, hyperglycemia must be corrected slowly, otherwise hypovolemia may be exacerbated by reduced refill. Parenteral nutrition or elemental diet is now being used with increasing frequency as a primary source of caloric support in patients with cardiac disease. The high protein load is metabolized with the resultant nitrogen excretion in the urine principally as osmotically active urea." At nearly maximal concentrating power of the kidney, 40 to 60 m1 of water excretion is required for each gram of nitrogen metabolized. Thus this high obligatory urine volume leads to dehydration. Once dehydration is established, hyperglycemia is aggravated and causes cellular dehydration, which suppresses the production of insulin and leads, in its turn, to hyperosmolar hyperglycemic nonketotic diabetic coma. Hypoxemia has not been included as a symptom of hyperosmolar hyperglycemic nonketotic diabetic coma in the literature. However, in Patient 11 low arterial oxygen tension persisted until hyperosmolar hyperglycemic nonketotic diabetic coma subsided. The wedge pressure denied cardiac origin. There were also no significant alterations in plasma protein concentration. Patient 5 also had hypoxemia and it was ascribed to a cardiac origin. These two patients are the only patients about whom hypoxemia was described in association with this disorder. However, a few articles have reported the occurrence of pulmonary edema of noncardiac origin in diabetic ketoacidosis. Two patients had pulmonary edema, which was attributed partly to increased permeability of pulmonary capillary membranes of diabetic origin." Another patient had two episodes of pulmonary edema attributed the increased permeability to pulmonary microvascular diabetic angiopathy." Vracko, Thorning, and Huang" observed that basal laminae of alveoli were significantly thicker in diabetic than control subjects. If diabetic predisposition causes the thickening and increased alveolar permeability, it is likely that patients subject to hyperosmolar hyperglycemic nonketotic diabetic coma are also susceptible to pulmonary edema of diabetic origin for the same reason as in diabetic ketoacidosis. This hypoxemia is usually treated by restricting fluid intake because of a working diagnosis of heart failure, and this restriction leads to dehydration. Hypernatremia in the presence of polyuria may be a

Volume 91 Number 6 June, 1986

Hyperosmolar hyperglycemic nonketotic diabetic coma

key to identifying hyperosmolar hyperglycemic nonketotic diabetic coma. The serum sodium level increased in eight of nine patients (88.8%). Sodium is lost in urine, but loss of water is more prominent and eventually leads to hypematremia. Another key to identifying this disorder is increased or increasing BUN in the presence of polyuria. Vigorous correction of abnormalities such as hyperglycemia and hypematremia should be avoided. Insulin should be given to avoid abrupt decreases in blood glucose levels, because lowered blood glucose lowers blood osmolality. Vigorous therapy with insulin may also complicate hypoglycemia, cerebral edema, shock, and acute renal failure. Decline in blood sugar during the first 2 hours should be limited to 60 to 80 mg/dl." Despite extraordinary hyperglycemia, low-dose insulin infusion (2 to 5 units an hour) is best. In my experience 0.5 to 2 units an hour was sufficient to suppress hyperosmolar hyperglycemic nonketotic diabetic coma in survivors. Too hasty correction of serum sodium should also be avoided.

2

3

4

5

6

REFERENCES Mills Nl., Isom OW, Spencer FC: Elevated blood sugar levels during cardiopulmonary bypass. Circulation 43,44:Suppl 2:109, 1971 Evans CC, littler WA, Meade JB: Hyperosmolar hyperglycemic nonketotic diabetic coma complicating open heart surgery. Br Heart J 34:1075-1077, 1972 Brenner WI, Lansky Z, Engelman RM, Stahl WM: Hyperosmolar coma in surgical patients. An iatrogenic disease of increasing incidence. Ann Surg 178:651-654, 1973 Soejima K, Tsuchiya K, Yasuura K, !ida Y, Miwa I: A case of hyperosmolar hyperglycemic nonketotic diabetic coma following double valve replacement. J Jpn Assoc Thorac Surg 27:104-108, 1979 (in Japanese) Iwasaki M, Yoshitake T, Furuse A, Shimizu S, Saegusa M, Tada Y, Wada T: A case of acute hemorrhagic gastric ulcers and nonketotic hyperosmolar coma following mitral valve replacement. Kyobugeka 33:188-191, 1980 (in Japanese) Kidani M, Iida S, Sato H, Noto M: A case of hyperosmolar hyperglycemic nonketotic coma following mitral valve replacement. Kyobugeka 36:119-121, 1983 (in Japanese)

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7 Deleted in revision 8 Arieff AI, Carroll HJ: Nonketotic hyperosmolar coma with hyperglycemia. Clinical features, pathophysiology, renal function, acid-base balance, plasma-cerebrospinal fluid equilibria and the effects of therapy in 37 cases. Medicine 51:73-94, 1972 9 McCurdy DK: Hyperosmolar hyperglycemic nonketotic diabetic coma. Med Clin North Am 54:683-699, 1970 10 Gill GY, Sherif IH, Alberti MM: Management of diabetes during open heart surgery. Br J Surg 68: 171-172, 1981 II Elliott MJ, Gill GY, Home PD, Noy GA, Holden MP, George K, Alberti M: A comparison of two regimens for the management of diabetes during open-heart surgery. Anesthesiology 60:364-368, 1984 12 Fonseca Y, Phear DN: Hyperosmolar nonketotic diabetic syndrome precipitated by treatment with diuretics. Br Med J 284:36-37, 1982 13 Swerlick RA, Drucker NA, McCoy S, Pearce FJ, Drucker WR: Insulin effectiveness in hypovolemic dogs. J Trauma 21:1013-1021, 1981 14 Friedman SG, Pearce FJ, Drucker WR: The role of blood glucose in defense of plasma volume during hemorrhage. J Trauma 22:86-91, 1982 15 Doromal NM, Canter JW: Hyperosmolar hyperglycemic nonketotic coma complicating intravenous hyperalimentation. Surg Gynecol Obstet 136:729-732, 1973 16 Bivins BA, Hyde GL, Sachatello CR, Griffen wo Physiopathology and management of hyperosmolar hyperglycemic nonketotic dehydration. Surg Gynecol Obstet 154:534-540, 1982 17 Podolsky S: Hyperosmolar nonketotic coma in the elderly diabetic. Med Clin North Am 62:815-828, 1978 18 Lavine RL: Hyperosmolar hyperglycemic coma, Critical Care, WW Oaks, K Bharadwaja, DA Major, eds., New York, 1978, Grune & Stratton, Inc., pp 47-52 19 Sprung ci, Rackow EC, Fein IA: Pulmonary edema. A complication of diabetic ketoacidosis. Chest 77:687-688, 1980 20 Brune-Buisson CJl, Bonnet F, Bergeret S, Lemaire F, Rapin M: Recurrent high-permeability pulmonary edema associated with diabetic ketoacidosis. Crit Care Med 13:55-56, 1985 21 Yracko R, Thorning D, Huang TW: Basal laminae of alveolar epithelium and capillaries. Quantitative changes with aging and in diabetes mellitus. Am Rev Respir Dis 120:973-983, 1979 22 DeFronzo RA: Type II diabetic emergencies. Emerg Med 16:54-55, 1984