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The significance of measurement of osmolality in critically ill patients
Resuscitation 7, 215-219
The significance of measurement of osmolality in critically ill patients
A. VILLANI, A. BONDOLI, D. CAMAIONI, A. M. D’ALLESSANDRO, S. I. MAGALINI and E. SCRASCIA Universita Cattolica de1 Sacro Cuore, Istituto di Anestesiologia e Rianimazione, Largo Agostino Gemelli 8, 00168 Rome, Italy
Summary The plasma and urine osmolality and their ratios were measured in 774 patients in critical care. We found that changes in osmolality were related to the alterations of ratios of sodium ion, glucose, blood urea nitrogen and unknown metabolites, and this knowledge may be of therapeutic and prognostic value. Introduction Alterations in water and electrolytes balance are frequently observed in critically ill patients suffering from shock, septic states, renal failure etc., treated in an intensive care unit, so that it is very important to have standard criteria for monitoring the development of osmolal inbalance. Measurements of osmolal balance provide data to assess the clinical conditions of patients. This paper reports the plasma and urine osmolality in 774 critical care patients undergoing intensive treatment and its value in prognosis. Patients and methods Seven hundred and seventy-four critically ill patients have been considered for the overall study. In addition, data of 218 randomized subjects were subdivided according to their clinical conditions. Blood and urine samples were collected before initial therapy and at daily intervals while the patients were under intensive treatment. The plasma and urine osmolality were measured by the freezing-point depression method using a micro-osmometer (Knauer, C. Erba Ltd, Milano). The plasma concentrations of sodium ion, glucose and urea nitrogen were determined by standard laboratory methods. The disciminate osmolalities were calculated in the 218 subjects from the formulae previously reported (Villani, Bondoli, Magalini, Scrascia, Proietti & Ranieri, 1977). The urine/plasma osmolality ratios were calculated on 112 patients. The statistical significance of the data was measured by x2, the formula x2 =_S(x’/m), and its significance by the P value of Pearson, according to Fisher (1941). 215
216
A. VILLANI AND OTHERS
Table 1.
Statistical analysis of osmolality data for two groups of patients in critical care in whom hyperosmolality was either present or absent. For initial values in the group showing hyperosmolality x2 = 36.36 and for the group without hyperosmolality P
Hyperosmolality present Hyperosmolality absent Totals
Table 2.
Survival
Total
Initial
Final
Initial
Final
Initial
Final
155 166 321
209 112 321
122 331 453
61 392 453
211 441 774
210 504 114
Plasma osmolality of 218 patients grouped according to condition. Osmolality (mosmol/kg of water) Finalvalues
Shock Acute poisoning Polytrauma Postoperative Neuropathology Respiratory failure Heart failure Diabetic coma Myocardial infarction Acute renal failure Miscellaneous
Results
No. of cases
Initial values
Survival
Death
25 14 I 23 31 41 12 9 30 12 14
294 299 280 305 309 295 309 334 289 325 304
280 286 268 291 295 291 283 288 295 271 285
330 340 298 326 331 303 306 328 306 349 354
,
Data about hyperosmolal states were subdivided for analysis according to survival or death. Table 1 shows the statistical analysis of the data from the two groups of patients with respect to the presence or the absence of hyperosmolal state. There were significant correlations between the hyperosmolal state and death both at the time of admission to the intensive care unit as well as at the time of termination of therapy (P < 0.001). The plasma osmolality of 218 patients, subdivided into 11 groups according to their conditions, are shown in Table 2. The various associations of major osmotic factors (sodium ion, glucose, effect on hyperosmolal conditions as a percentage) are given in Fig. 1. The urine/plasma osmolality ratio has been calculated and plotted according to mortality only in a group of 122 patients and subdivided into two subgroups according to the presence of acute renal failure (Fig. 2).
OSMOLALITY
AND PROGNOSIS
217
Na*-Glut-BUN, Giuc-BUNII ,
---'
Glut-BUN-Aosme Glut-Aosm~,-Na+-Glucb Glut*--+ ~_____, BUNo-, Na+-Glut-BUN.Aosmr-' BUN-Aosmk
death I INITIAL
-
death
survival _ __-.. ._
survival
FINAL
BUN ? Na+-
AosmZ Na+-Glut-Aosm: Na+-Aosm? NatBUN-Aosmy Na+: c
0
Fig. 1. Percentage
weight
I
5
of various
10
osmotic
I
15
20
components
1
25
I
I
30
in hyperosmolal
100
states.
BUN.
%
Blood
urea
nitrogen.
Discussion
Attempts to establish criteria of diagnostic and/or prognostic significance represent one of the primary aims in an intensive care unit. It appears also of importance to assess the value of these criteria for a verification of the effectiveness of the clinical management. Previous reports have shown the great value of osmolal measurements as a monitoring parameter in critically ill patients (Holmes, 1962; Boyd & Mansberger, 1968; Boyd, Folk & Condon, 1970; Boyd & Baker, 1971; Magalini, Villani & Manni, 1975). Mattar, Weil, Shubin & Stein (1956) observed that patients with plasma osmolality above 340 mosmol/kg of water present a poor prognosis, and likelihood of rapid death from the hyperosmolal states is not reduced by the immediate application of specific intensive therapeutic measures. The high correlation between the presence of hyperosmolal status and eventual death, observed in our patients, appears to confirm this prognostic role of measurements of osmolality.
218
A. VILLANI AND OTHERS
admission
survival function: El: renal
renal function:
r&t , death normal insufficient
2.37t0.08 2.22t0.07
P
cases
83
39
62
6
21
33
Fig. 2. Urine/plasma osmolality ratios and final outcome observed in patients with or without acute renal failure.
The presence of an initial hyperosmolal status seemed to influence the clinical course of the illness (Table 1) except when efficient corrective measures were applied and succeeded in modifying this condition. The group of patients with high initial osmolal values that survived (50%) was that in which this parameter was successfully corrected (Table 1). Furthermore, the analysis of absolute values of Pearson correlation coefficient (initial= 36, 36; fmal=218, 32) indicated that the persistence of plasma hyperosmolality was a bad omen for the final outcome. The study of osmolal balance in the groups subdivided according to the pathological states showed that an evident initial alteration of plasma osmolality was consistently present only in those with diabetes mellitus and acute renal failure. Obviously, these coneitions are characterized by severe alterations of specific osmotic components (glucose and blood urea nitrogen). It was also observed that a moderate initial increase in plasma osmolal value were found in neurological diseases and in acute or chronic heart failures. In neurological conditions this change appeared to be related to the alterations of sodium ion balance and/or to the treatments by osmotic diuresis; in heart conditions, the osmolar modification may be attributed to secondary haemodynamic changes influencing renal function.
OSMOLALITY AND PROGNOSIS
219
The strong correlation between plasma osmolality and final outcome observed in the overall study was also present when the single pathological groups were individually considered. In many pathological conditions such as uraemia, hepatic failure, diabetic keto-acidosis and shock, differences between measured and calculated plasma osmolality of about 40 mosmol have been observed (Rubin, Bravenman & Dexter, 1956; Bondoli, Villani, Schiavello, De Francisci & Adario, 1976; Villani, D’Alessandro, Magalini, Barbi & Bondoli, 1978). It may be postulated that unknown osmotic components (perhaps endotoxins) are produced in these conditions and that a fatal outcome frequently occurs when their concentrations became so high to cause a change in osmolality exceeding 40 mosmol/kg of water. The various associations of osmotic factors observed in hyperosmolar states (Fig. 1) showed that concomitance of changes in sodium ion, glucose and blood urea nitrogen concentrations is of even greater prognostic importance. It is also suggestive that changes in Na+ alone in our patients did not cause hyperosmolality. In critically ill patients, probably, the metabolic derangements are so complex that they produce a severe general water-electrolyte imbalance. The urine/plasma osmolality ratios seem strongly related to the clinical evolution in patients with acute or chronic renal failure (Fig. 2). This ratio appears useful to evaluate the tubular function since it is not affected by the presence of macromolecular compounds in the urine. In conclusion, in the clinical biochemistry of critical care patients it appears extremely difficult to attribute changes in osmolality to a single cause, since these represent one of the many consequences occurring in the final stage of many acute conditions. However, the osmolal balance is important because of its general therapeutic and prognostic implications. References Bondoli, A., Villani, A., Schiavello, R., De Franc&i, G. & Addario, C. (1976) Modihcazioni dell’osmolalita plasmatica durante circolazione extracorporea. Acta Anesth. Ital. 27, 3255344. Boyd, D. R. & Baker, R. J. (1971) Osmometry: a new bedside laboratory aid for the management of surgical patients. Surg. Clin. North Am. 51, 241-250. Boyd, D. R., Folk, F. A. & Condon, R. E. (1970) Predictive value of serum osmoiality in shock following trauma. Surg. Forum 21, 32-33. Boyd, D. R. & Mansberger, A. R., Jr (1968) Serum water and osmolal change in hemorrhagic shock: an experimental and clinical study. Ann. Surg. 34. 744749. Fisher, A. (1941) Statistical Methodsfor Research Workers, 8th edn, pp. 76-111. Oliver and Boyd, London. Holmes, J. H. (1962) Measurement ofOsmolality in Serum. Urine and Other Biological Fluids by the Freezing Point Determination. Pre-Workshop Manual of the Workshop Studies. Chicago, American Society of Clinical Pathologists,
on Urinalysis
and Renal Function
Magalini, S. I., Villani, A. & Manni, C. (1975) La diurese forcee et le rapport osmolalite serum-urinaire. Bull. de Med. Leg. de Toxicol. Med. 85, 361-367. Mattar, J. A., Weil, M. H., Shubin, H. S. & Stein, L. (1956) Cardiac arrest in the critically ill. Hyperosmolal states following cardiac arrest. Ann. J. Med. 56, 1622168. Rubin, A. L., Bravenman, W. S. & Dexter. R. L. (1956) The relationship between plasma osmolality concentration in disease states. C/in. Res. Proc. 4, 1299132. Villani, A.. D’Alessanbro, A. M., Magahni, S. I., Barbi, S. & Bondoli, A. (1978) Osmolality measurements in heart disease. Resuscitation 6, 77-85. Villani. A., Bondoli, A., Magalini, S. I., Scrascia, E., Pronetti, R. & Ranieri, R. (1977) Ruolo delle misure osmometriche in terapia intensiva. Rass. Chni. Sci. 34, 3313.
The significance of measurement of osmolality in critically ill patients
A. VILLANI, A. BONDOLI, D. CAMAIONI, A. M. D’ALLESSANDRO, S. I. MAGALINI and E. SCRASCIA Universita Cattolica de1 Sacro Cuore, Istituto di Anestesiologia e Rianimazione, Largo Agostino Gemelli 8, 00168 Rome, Italy
Summary The plasma and urine osmolality and their ratios were measured in 774 patients in critical care. We found that changes in osmolality were related to the alterations of ratios of sodium ion, glucose, blood urea nitrogen and unknown metabolites, and this knowledge may be of therapeutic and prognostic value. Introduction Alterations in water and electrolytes balance are frequently observed in critically ill patients suffering from shock, septic states, renal failure etc., treated in an intensive care unit, so that it is very important to have standard criteria for monitoring the development of osmolal inbalance. Measurements of osmolal balance provide data to assess the clinical conditions of patients. This paper reports the plasma and urine osmolality in 774 critical care patients undergoing intensive treatment and its value in prognosis. Patients and methods Seven hundred and seventy-four critically ill patients have been considered for the overall study. In addition, data of 218 randomized subjects were subdivided according to their clinical conditions. Blood and urine samples were collected before initial therapy and at daily intervals while the patients were under intensive treatment. The plasma and urine osmolality were measured by the freezing-point depression method using a micro-osmometer (Knauer, C. Erba Ltd, Milano). The plasma concentrations of sodium ion, glucose and urea nitrogen were determined by standard laboratory methods. The disciminate osmolalities were calculated in the 218 subjects from the formulae previously reported (Villani, Bondoli, Magalini, Scrascia, Proietti & Ranieri, 1977). The urine/plasma osmolality ratios were calculated on 112 patients. The statistical significance of the data was measured by x2, the formula x2 =_S(x’/m), and its significance by the P value of Pearson, according to Fisher (1941). 215
216
A. VILLANI AND OTHERS
Table 1.
Statistical analysis of osmolality data for two groups of patients in critical care in whom hyperosmolality was either present or absent. For initial values in the group showing hyperosmolality x2 = 36.36 and for the group without hyperosmolality P
Hyperosmolality present Hyperosmolality absent Totals
Table 2.
Survival
Total
Initial
Final
Initial
Final
Initial
Final
155 166 321
209 112 321
122 331 453
61 392 453
211 441 774
210 504 114
Plasma osmolality of 218 patients grouped according to condition. Osmolality (mosmol/kg of water) Finalvalues
Shock Acute poisoning Polytrauma Postoperative Neuropathology Respiratory failure Heart failure Diabetic coma Myocardial infarction Acute renal failure Miscellaneous
Results
No. of cases
Initial values
Survival
Death
25 14 I 23 31 41 12 9 30 12 14
294 299 280 305 309 295 309 334 289 325 304
280 286 268 291 295 291 283 288 295 271 285
330 340 298 326 331 303 306 328 306 349 354
,
Data about hyperosmolal states were subdivided for analysis according to survival or death. Table 1 shows the statistical analysis of the data from the two groups of patients with respect to the presence or the absence of hyperosmolal state. There were significant correlations between the hyperosmolal state and death both at the time of admission to the intensive care unit as well as at the time of termination of therapy (P < 0.001). The plasma osmolality of 218 patients, subdivided into 11 groups according to their conditions, are shown in Table 2. The various associations of major osmotic factors (sodium ion, glucose, effect on hyperosmolal conditions as a percentage) are given in Fig. 1. The urine/plasma osmolality ratio has been calculated and plotted according to mortality only in a group of 122 patients and subdivided into two subgroups according to the presence of acute renal failure (Fig. 2).
OSMOLALITY
AND PROGNOSIS
217
Na*-Glut-BUN, Giuc-BUNII ,
---'
Glut-BUN-Aosme Glut-Aosm~,-Na+-Glucb Glut*--+ ~_____, BUNo-, Na+-Glut-BUN.Aosmr-' BUN-Aosmk
death I INITIAL
-
death
survival _ __-.. ._
survival
FINAL
BUN ? Na+-
AosmZ Na+-Glut-Aosm: Na+-Aosm? NatBUN-Aosmy Na+: c
0
Fig. 1. Percentage
weight
I
5
of various
10
osmotic
I
15
20
components
1
25
I
I
30
in hyperosmolal
100
states.
BUN.
%
Blood
urea
nitrogen.
Discussion
Attempts to establish criteria of diagnostic and/or prognostic significance represent one of the primary aims in an intensive care unit. It appears also of importance to assess the value of these criteria for a verification of the effectiveness of the clinical management. Previous reports have shown the great value of osmolal measurements as a monitoring parameter in critically ill patients (Holmes, 1962; Boyd & Mansberger, 1968; Boyd, Folk & Condon, 1970; Boyd & Baker, 1971; Magalini, Villani & Manni, 1975). Mattar, Weil, Shubin & Stein (1956) observed that patients with plasma osmolality above 340 mosmol/kg of water present a poor prognosis, and likelihood of rapid death from the hyperosmolal states is not reduced by the immediate application of specific intensive therapeutic measures. The high correlation between the presence of hyperosmolal status and eventual death, observed in our patients, appears to confirm this prognostic role of measurements of osmolality.
218
A. VILLANI AND OTHERS
admission
survival function: El: renal
renal function:
r&t , death normal insufficient
2.37t0.08 2.22t0.07
P
cases
83
39
62
6
21
33
Fig. 2. Urine/plasma osmolality ratios and final outcome observed in patients with or without acute renal failure.
The presence of an initial hyperosmolal status seemed to influence the clinical course of the illness (Table 1) except when efficient corrective measures were applied and succeeded in modifying this condition. The group of patients with high initial osmolal values that survived (50%) was that in which this parameter was successfully corrected (Table 1). Furthermore, the analysis of absolute values of Pearson correlation coefficient (initial= 36, 36; fmal=218, 32) indicated that the persistence of plasma hyperosmolality was a bad omen for the final outcome. The study of osmolal balance in the groups subdivided according to the pathological states showed that an evident initial alteration of plasma osmolality was consistently present only in those with diabetes mellitus and acute renal failure. Obviously, these coneitions are characterized by severe alterations of specific osmotic components (glucose and blood urea nitrogen). It was also observed that a moderate initial increase in plasma osmolal value were found in neurological diseases and in acute or chronic heart failures. In neurological conditions this change appeared to be related to the alterations of sodium ion balance and/or to the treatments by osmotic diuresis; in heart conditions, the osmolar modification may be attributed to secondary haemodynamic changes influencing renal function.
OSMOLALITY AND PROGNOSIS
219
The strong correlation between plasma osmolality and final outcome observed in the overall study was also present when the single pathological groups were individually considered. In many pathological conditions such as uraemia, hepatic failure, diabetic keto-acidosis and shock, differences between measured and calculated plasma osmolality of about 40 mosmol have been observed (Rubin, Bravenman & Dexter, 1956; Bondoli, Villani, Schiavello, De Francisci & Adario, 1976; Villani, D’Alessandro, Magalini, Barbi & Bondoli, 1978). It may be postulated that unknown osmotic components (perhaps endotoxins) are produced in these conditions and that a fatal outcome frequently occurs when their concentrations became so high to cause a change in osmolality exceeding 40 mosmol/kg of water. The various associations of osmotic factors observed in hyperosmolar states (Fig. 1) showed that concomitance of changes in sodium ion, glucose and blood urea nitrogen concentrations is of even greater prognostic importance. It is also suggestive that changes in Na+ alone in our patients did not cause hyperosmolality. In critically ill patients, probably, the metabolic derangements are so complex that they produce a severe general water-electrolyte imbalance. The urine/plasma osmolality ratios seem strongly related to the clinical evolution in patients with acute or chronic renal failure (Fig. 2). This ratio appears useful to evaluate the tubular function since it is not affected by the presence of macromolecular compounds in the urine. In conclusion, in the clinical biochemistry of critical care patients it appears extremely difficult to attribute changes in osmolality to a single cause, since these represent one of the many consequences occurring in the final stage of many acute conditions. However, the osmolal balance is important because of its general therapeutic and prognostic implications. References Bondoli, A., Villani, A., Schiavello, R., De Franc&i, G. & Addario, C. (1976) Modihcazioni dell’osmolalita plasmatica durante circolazione extracorporea. Acta Anesth. Ital. 27, 3255344. Boyd, D. R. & Baker, R. J. (1971) Osmometry: a new bedside laboratory aid for the management of surgical patients. Surg. Clin. North Am. 51, 241-250. Boyd, D. R., Folk, F. A. & Condon, R. E. (1970) Predictive value of serum osmoiality in shock following trauma. Surg. Forum 21, 32-33. Boyd, D. R. & Mansberger, A. R., Jr (1968) Serum water and osmolal change in hemorrhagic shock: an experimental and clinical study. Ann. Surg. 34. 744749. Fisher, A. (1941) Statistical Methodsfor Research Workers, 8th edn, pp. 76-111. Oliver and Boyd, London. Holmes, J. H. (1962) Measurement ofOsmolality in Serum. Urine and Other Biological Fluids by the Freezing Point Determination. Pre-Workshop Manual of the Workshop Studies. Chicago, American Society of Clinical Pathologists,
on Urinalysis
and Renal Function
Magalini, S. I., Villani, A. & Manni, C. (1975) La diurese forcee et le rapport osmolalite serum-urinaire. Bull. de Med. Leg. de Toxicol. Med. 85, 361-367. Mattar, J. A., Weil, M. H., Shubin, H. S. & Stein, L. (1956) Cardiac arrest in the critically ill. Hyperosmolal states following cardiac arrest. Ann. J. Med. 56, 1622168. Rubin, A. L., Bravenman, W. S. & Dexter. R. L. (1956) The relationship between plasma osmolality concentration in disease states. C/in. Res. Proc. 4, 1299132. Villani, A.. D’Alessanbro, A. M., Magahni, S. I., Barbi, S. & Bondoli, A. (1978) Osmolality measurements in heart disease. Resuscitation 6, 77-85. Villani. A., Bondoli, A., Magalini, S. I., Scrascia, E., Pronetti, R. & Ranieri, R. (1977) Ruolo delle misure osmometriche in terapia intensiva. Rass. Chni. Sci. 34, 3313.