PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION DURING VENTILATOR TREATMENT

Brit. J. Anaesth. (1971), 43, 460

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION DURING VENTILATOR TREATMENT BY

P. M. GETT, E. SHERWOOD JONES AND G. F. SHEPHERD SUMMARY

"When you have eliminated all which is impossible, then whatever remains, however improbable, must be the truth." (Sherlock Holmes in The Blanched Soldier)

Prolonged intermittent positive pressure ventilation (IPPV) is used in this unit to treat crushing injuries of the chest, poisoning, pneumonia, chronic lung disease, asthma, myasthenia gravis, polyneuritis, tetanus and postoperative respiratory failure. The changes in the lungs, assessed by daily radiographs, fall into two groups. In the first group, the radiograph taken on admission shows abnormal signs due to injury, primary infection, chemical inflammation or absorption collapse; in the second group the radiological signs are normal when IPPV is started. Either group may develop radiological signs during IPPV and it is often difficult to determine their cause. Pneumothorax, effusion, collapse of a segment or whole lung can usually be recognized. It is not always possible to decide the pathological processes causing other widespread opacities in the lung fields and enlarged hila; signs which strongly suggest pulmonary oedema. When these signs develop during IPPV they are associated with deterioration of the patient's condition and lung

physiology. The physiological events are; compliance falls and the oxygen gradient increases; at a later stage there is hypercapnia and hypoxaemia, despite large minute volumes with high concentrations of inspired oxygen. The electrocardiograph may show right axis deviation or the criteria of right ventricular strain. The heart may arrest and it is then rarely possible to restore an effective heart beat. The histological changes in the lungs of such patients were described by Ashbaugh and associates (1967), Castleman and McNeely (1967) and Linton, Walker and Spoerel (1965), and show a striking similarity to those of experimental pulmonary oxygen toxicity (Smith, 1899; Cederberg, Hellsten and Miorner, 1965). It was natural, therefore, to deduce that the use of high inspired concentrations of oxygen during IPPV was the cause of the pulmonary oedema. Since 1968 we have followed the current practice, P. M.

GETT,* M.B.,B.S., F.F.A.R.C.S., E. SHERWOOD

JONES, PH.D., F.R.C.P., D.T.M.&H., Dept. of Clinical

Pharmacology, (University of Liverpool) and Intensive Care Unit, Whiston Hospital, Prescot, Lancashire; G. F.

SHEPHERD, M.A.,M.B.(DUBLIN), D.M.R-D.,

Consul-

tant Radiologist, Whiston Hospital, Prescot, Lancashire. * Present address: 31 Cotswold Street, Strathneld, N.S.W., Australia.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

Intermittent positive pressure ventilation was used to treat seven adult patients with respiratory failure due to chest injury, paralysis, pulmonary infection or inhalation of vomit. Of these seven patients, six recovered. The inspired oxygen tension was maintained in the range of 200-300 mm Hg whenever possible. Metabolic balance studies were correlated with daily radiographs of the chest. Retention of sodium occurred in all seven patients, occurring within a few days of starting IPPV in four patients. Radiographs of four patients showed signs of pulmonary oedema developing during IPPV, and the development of pulmonary oedema correlated with periods of sodium retention. During IPPV a diuretic usually caused a natriuresis, and in four instances this was followed by a reduction in the signs of pulmonary oedema. The physiological mechanisms by which IPPV caused sodium retention and pulmonary oedema are not known. Diuretics should be given during IPPV when, in the absence of dehydration, sodium balance is positive for more than 3 days or when the chest radiograph shows signs of pulmonary oedema.

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION

PATIENTS AND METHODS

Patients. There were four women and three men with acute respiratory failure treated by IPPV through a tracheostomy. Ventilation was continued for a mean period of 181 days. Table I summarizes the clinical findings. One patient died from infection of the respiratory tract with consolidation and multiple abscesses. Biochemical. pH, PaCO25 PaO25 were measured by the methods described in a previous paper (Finnegan and Jones, 1969). Sodium and potassium were measured on an internal-standard flame photometer and chloride measured electrometrically. The 95 per cent confidence limits for the plasma electrolytes of healthy subjects were: sodium 136-147, potassium 3.7-4.6, chloride 100-110 m.equiv/1. (Thompson and Jones, 1965). Metabolic balance was obtained by the methods used in this laboratory since 1958 (Jones and Sechiari, 1963; Jones and Peaston, 1966). The data were collected over 24-hour periods starting

at 8 a.m. each day. The input and output of water, sodium and potassium were charted above and below a baseline. With the exception of infusions used during resuscitation, the patients were given an intragastric diet consisting of Complan (Glaxo) 150 g, glucose 150 g, Celevac (HarkerStagg) 3 g, and water 1.6 1. This diet provided a daily intake of 2,580 calories, nitrogen 14.4, sodium 66 m.equiv, potassium 84 m.equiv, and chloride 60 m.equiv. Alternatively, an intravenous diet was given consisting of 20 per cent Intralipid, Aminosol-fructose-ethanol, 10 per cent Aminosol (Vitrum) and supplements of potassium chloride and vitamins (Peaston, 1966). When possible, the balance data obtained during IPPV were compared with the results on the first few days after stopping IPPV. In this way the patient served as his own control. A positive balance for sodium was recorded when the measured intake exceeded the output by 30 m.equiv or more. A natriuresis was recorded when there was either a negative balance of 30 m.equiv or more, or threefold increase in urinary sodium over that of the preceding day (fig. 1). A positive or negative balance for water was defined as a difference of 1.5 or more litres between the intake and output. A positive or negative balance for potassium was recorded when there was a difference of 30 m.equiv or more between the intake and output. These results were compared with those obtained by Peaston (1967) who gave a standard intragastric diet to healthy subjects (table II). This diet was routinely used during TPPR in this unit until sodium retention during IPPR was discovered. Since that time the intake of water, and more especially of sodium, has been reduced. The amounts of sodium and water given by Peaston

TABLE I

Patient 1 2 3

Age (yr) 42 20

5

17 33 34

6 7

26 68

4

Clinical findings and the results of treatment. Duration of IPPV Diagnosis (days) Polyneuritis, pulmonary infection 53 31 Appendicitis, peritonitis, bowel fistula, subphrenic abscesses, pulmonary infection 9 Myasthenia gravis 8 Chest injury Inhalation of vomit, acute poisoning, 9± schizophrenia Chest injury, torn liver 7i Polyneuritis, ischaemic heart disease 22

Results of treatment Died Lived Lived Lived Lived Lived Lived

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

which is to use only sufficient oxygen to maintain the Pa 02 in the range of 90-100 mm Hg. This practice has not, however, prevented the development of the signs of pulmonary oedema. In 1966 Dr P. Finnegan in our unit noticed increasing oedema during IPPV used to treat acute respiratory failure due to chronic lung disease (Finnegan and Jones, 1969). In 1969 one of us (E.S.J.) observed very low concentrations of sodium in the urine during IPPV. We have now obtained evidence that IPPV causes sodium retention, and that this may in turn cause pulmonary oedema.

461

462

BRITISH JOURNAL OF ANAESTHESIA

are larger than those received by some of the patients in the present study. Our criteria for positive or negative balance for water or electrolyte are approximately twice those of Peaston and are therefore highly significant. 150 i -

c/)E

100 150 L

I—

TABLE

III

Radiological terminology.

o C CD

-Q

Signs

Homogeneous opacity

Uniform opacity in part or whole of a lung field Circular opacity of 2-3 cm diameter Increase in the hilar shadows, moderate ( + ) or considerable ( + + ) Opacities (homogeneous or irregular) in part or whole of a lung field with air bronchogram Self-descriptive

Woolly opacity

B

1 Upper. Criteria for positive sodium balance and natriuresis. Input and output all charted above and below the baseline respectively. Lower. Mean N a / K ratio during positive sodium balance or natriuresis. A, Sodium balance. B, Positive balance C, Natriuresis. D, Natriuresis. FIG.

TABLE

Enlarged hila Consolidation

Prominent vascular pattern

II

Balance data on healthy subjects (from Peaston 1967). Intragastric diet of Complan-glucose (seven healthy subjects, mean time 4-6 days).

Intake per day Output in urine Balance

Term

Water (1.)

Sodium (m.equiv)

Potassium (m.equiv)

2.56 1.77 0.79

116 105 11

84 66 18

Radiological. Chest radiographs were taken with a mobile machine (Dean 38). The radiographs were taken at a fixed distance of 1.2 m and the radiographic factors for each patient were standardized. The radiographs were examined by the doctors treating the patients and, at the end of the treatment, by the radiologist. The films were reported without knowledge of the clinical state or treatment. Each series was examined on three or more occasions by the radiologist without reference to his previous comments. The abnormal findings in the

Therapeutic. The patients were treated in a general intensive therapy unit by a team of nurses, physicians and anaesthetists (Lancet, 1964). The treatment of shock by infusions or by blood transfusions was controlled by the arterial blood pressure recorded with a sphygmomanometer, and the central venous pressure recorded with a catheter in the superior or inferior vena cava (Sykes, 1963). The patient was nursed with the head and trunk raised to an angle of 30 degrees when the cough was effective in raising sputum, and with the trunk flat when the cough was ineffective. Tracheostomy was performed within 48 hours of starting IPPV and tracheostomy care was based on the methods described by Smith (1967). The Cape ventilator was used for controlled ventilation and the Bird Mark 8 ventilator was used for assisted ventilation. A subatmospheric pressure (expiratory assistance) was used during shock or when the Valsalva reflex was blocked. Crushing injuries

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

Ij

100 50 0 50

radiographs were recorded in simple descriptive terms as listed in table i n . The term consolidation is used to imply a state of the lung in which the airways are patent and the alveoli contain fluid, either exudate or transudate. When this preliminary work was completed, the reports were correlated with the primary pathological process in the lungs, for example infection, injury, or inhalation of vomit. The reports were also correlated with specific treatment, for example aspiration of an effusion, clearing of a bronchus, or diuretic therapy. This enabled us to establish the probable interpretation of the radiological signs.

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION of the chest are treated by "internal pneumatic stabilization", using deliberate hyperventilation (Avery, Morch and Benson, 1956). Muscle relaxants were used only when the relief of pain, hyperventilation, clearing of the airways and resetting of the ventilator failed to control the patient's respiration. Oxygen was added to the inspired air in amounts sufficient to keep the Pa0= within the range 90-100 mm Hg, bearing in mind that concentrations above 70 per cent (Pi02 approx. 500 mm Hg) can, if used for prolonged periods, cause pulmonary oxygen toxicity (Barach, 1926; Smith, 1899). Inspired tensions of oxygen are shown in figure 2, where it will be seen that a value of Pi 03 above 500 mm Hg was used for only short periods. The diuretics used were frusemide (40 mg) or clopamide (20 mg).

463

26272829303132333435363738394041424344454647484950515253 -IPPR(Cape)

Day

. . Bird Spontaneous air-mtx respiration

P2 4 5 6 7 8 91011121314151617181920212223242526 IPPR(Cape)

Day

RESULTS

Metabolic balance. The data on six of the seven patients are summarized in table IV. Balance studies were started late in the treatment of the first patient. In three patients complete balance data were obtained both during and after IPPV. Results were obtained on a total of 129 patient-days. The most striking abnormality was the positive balance for sodium which was demonstrated in all patients. The sodium balance became positive 2-3 days after starting IPPV. The concentration of sodium in the urine fell to values in the range of 5-15 m.equiv/1. and the ratio of Na/K was within the range of 0.1-0.3. During weaning from or after stopping IPPV, three of the patients had a natriuresis or reached a balance for sodium. In the sixth patient, retention was seen during IPPV and also 4-6 days after stopping IPPV, when a spontaneous natriuresis took place. The seventh patient, who had overt congestive cardiac failure, also continued to retain sodium after IPPV. The data on the second patient were incomplete because of incontinence on 12 days. However, urine analysis showed very low concentrations of sodium. Of sixteen daily samples collected during IPPV, the sodium concentration was 10 m.equiv/ 1. or less on eleven occasions and the Na/K ratio was 0.1 or less on the samples. The second important finding was that the urinary sodium returned to normal values when IPPV was stopped, the mean sodium concentration rising to 53

1 2 3 4 5 6 7 8 9 1011121314151617

600

Day

—IPPR(Cape)—Bird air-mix

400 200 P5 Y 2 ' 3 V 5 V 7 ' 8 9' Day IPPR(Cape)

__

"H.2 Humidified O2 spontaneous respiration

P6 5 6 7 8 9 1011 '121314151617 18 Day -IPPR(Cape) 600

Humidified C»2 spontaneous respiration Bird

Bird air-mix

Bird air-mix

400 200 1 2 3 4 5 6 7 8 9 10111213141516171819202122232425262728293031323334 Day p7

FIG. 2 Showing inspired and arterial oxygen tensions on the patients. B = Bird ventilator. Stippled portion = Plo2. Black line=Pa02.

m.equiv/1. and the Na/K ratio rose to a mean value of 1.1 ( n = l l ) . A diuretic was given to four of the patients on 16 occasions because of pulmonary oedema and on 13 occasions to restore sodium balance in three patients who did not show pulmonary oedema. Two patients (numbers 3 and 5) were given a diuretic on the first day of IPPV because of oliguria. On each of the 29 occasions the diuretic induced a natriuresis and the N a / K ratio rose eight to tenfold.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

P3 1 ' 2 ' 3 V 5 6'7 8'9 10111213' Day IPPR(Cape)

TABLE I V

Metabolic balance data on six of the patients. Patient No.

Age (yr)

IPPR (No. of days) Result

Diagnosis

33

Chest injury

34

Inhalation of vomit, acute poisoning, schizophrenia Chest injury, torn liver Polyneuntis, ischaemic heart disease

26 68

Positive (Day)

26, 27, 28, 32, 36, 38-40, 44, 51, 53, 1,4,8

5

5

8, 12

Negative (Day)

36

31, 39^»3, 45,51.53

32, 36, 38

3

2,3, 5-7 4, 8, 9, 11, 12 2,4, 7-9

4

35, 37, 38, 45-53

y

Lived

S

Lived

3, 5-7, 13 3, 4, 8, 9

Lived

1, 3,5

6-9

1,6

I

Lived

5-10, 14-16 3, 5, 6, 9-11, 15-17, 21,23,29

11, 12, 18

3, 11, 12

8.9

7, 12, 13, 24, 25, 31, 33,34

7, 12. 13, 24, 25. 27, 28, 30, 31-34

23

22

Lived

26-29, 32, 36, 38, 40-44 1,4, 8

Positive (Day;

Died

53

Potassium balance

Water balance Diuretic (Day)

Natriuresis (Day)

Negative (Day)

12

6, 7, 10. 12-15 2, 10, 15-18, 21-23, 27-29 31-33

2,5,7 13 3,5,6

12

P6

200

r

•5 100 -

Urine concentration (m.equiv IV

9 10 11 12 13 14 15 16 17 18 Day

Na 45 I 5 . 17 126 K

Na

6

62 36 36 37 65 56 42 24 55 48 47 64 35 31

5

6

7 23 33 114 118 • » 10 8 54 53 79

Plasma concentration (m equiv./l.) Na 144 143 150 - 136 135 136 133 133 134 - 132 133 136 K 31 2 7 3-4 - 38 36 3 5 27 26 2 9 - 4 7 37 3 3

FIG. 3 Metabolic balance on patient No. 6. Input and output are charted above and below the baseline respectively. D = diuretic. B=Bird ventilator. T=blood transfusion.

17 14 16 28 34 41 38 34 32 34 50 70 48 44 46 47 58 77 70 73 56 60

Plasma concentration (m.equiv./l.)

Urine concentration (m equiv. / I.) K

65 78 69 97

Na

lit

139

137 13S

124

K

32

36

29 4-2

3-7

FIG. 4 Metabolic balance on patient No. 4. Input and output are charted above and below the baseline respectively. D=diuretic. B=Bird ventilator. Square at top of chart=data on output incomplete.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

17

Polyneuntis pulmonary infection Myasthenia gravis

42

Positive sodium balance (Day)

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION

Plasma concentrations of sodium and potassium and blood urea values. A total of 42 measurements of the plasma sodium and potassium were made, the number of determinations on each patient increasing as the investigation proceeded. Examples of the results are shown on the metabolic balance charts (figs. 3 and 4). Of the plasma sodium values 33 were within, or near to, the normal range. Severe hyponatraemia was found once (patient 7, day 29) and was attributed to diuretic therapy. Severe hypernatraemia was observed four times on patient 5 (days 2, 4, 5 and 6) and was not explained. No samples showed hyperkalaemia. Severe hypokalaemia was observed twice. In patient No. 5 hypokalaemia was found on day 4 but the cause was not evident from the potassium balance. In patient 7, hypokalaemia occurred (day 26) before several days of positive potassium balance. TABLE: V Blood urea values on the patients.

The blood urea values are given in table V. The blood urea was normal in four patients and three patients (Nos. 4, 5, 7) had moderate uraemia. Blood-gas tensions. The Pa 0? was usually maintained at about 100 mm Hg. Hypoxaemia occurred in patient No. 1 during episodes of bacterial shock. The fifth patient had hypoxaemia during the first 3 days of IPPV and on day 6; this was attributed to pulmonary oedema. The oxygen gradient (A-a Doa) for all patients was examined. The results varied from day to day and during the day, but no correlation was found with the metabolic or radiological findings. Patients 1 and 2 showed hypercapnia despite large minute volumes; the mean PaCo2 values were 52 and 48 mm Hg respectively. Hypocapnia due to deliberate hypoventilation was found in four patients' Pa0o2 (25 + 2.6 mm Hg). Radiology. The findings are summarized in tables VI and VII The radiographs taken at the start of IPPV all showed some abnormality. Patients 1, 4 and 7 had signs of a linear atelectasis which was quickly and completely cleared by suction and chest physiotherapy. Patients 4 and 6 each had a pneumothorax which was drained; these patients also had rib fractures. During IPPV patients 1 and 2 showed consolidation, and this was attributed to bacterial pneumonia. We diagnosed pulmonary oedema on the following signs: enlarged hila, woolly opacities, prominent vascular pattern and homogeneous opacities (table III). These signs, in varying combinations, were found in four patients (Nos. 3, 5, 6 and 7) on a total of 49 days. In patients 1 and 2, the signs of pulmonary oedema were not seen but may have been obscured by those of consolidation.

Blood urea (mg/100 ml) TABLE VI No.

No. of observations

1 2 3 4 5 6 7

12 13 6 9 11 17 15

Patient

Mean 40 42 31 66 50 41 75

Values over 60 mg/100 ml 2 2 0 3 3 1 10

Summary of radiological findings in the seven patients whilst under treatment. Radiological findings

Patient No.

Pulmonary oedema Consolidation Segmental absorption collapse Pneumothorax Effusion or empyema Abscesses

3, 1, 1, 1, 2, 1

5, 6, 7 2 3, 4 4, 6 4, 6

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

During IPPV water balance was positive on 8 days only; on 6 occasions sodium balance was also positive. It follows that on the days when sodium balance was positive there was a corresponding positive water balance on only 6 days. There was no systematic change in potassium balance. The balance was positive on 46 days and negative on 12 days, and there was potassium balance on 71 days. Diuretics caused a negative potassium balance. The balance data of the sixth patient are shown in figure 3 and described under Case Report. The results on patient number 4 are shown in figure 4. This balance chart illustrates how a diuretic was used to restore sodium balance in a patient without pulmonary oedema.

465

468

BRITISH JOURNAL OF ANAESTHESIA TABLE

VII

Correlations between sodium balance and radiological evidence of pulmonary oedema. Patient No. 3

IPPV (days) 9

5' S

9i 7i

positive

negative

Normal radiograph

increasing or constant

3, 5-7, 13

1, 4, 8

2-4

5-8, 12

1, 3, 5 5-10, 14-16

6-9

12

11, 12, 18

20 (except for pleural thickening)

1-2 7-11, 16-18

33 5, 6, 9-11, 15-17, 21, 23, 29

7, 12, 13, 24, 25, 31, 33, 34

3, 14-23, 26, 34

The following report (patient No. 6) illustrates sodium retention and pulmonary oedema developing during IPPV, and the clearing of this oedema following a natriuresis.

4-5, 12-13, 24, 27-30

decreasing 10, 13-15 3-11 12-13, 19-20 6-7, 25, 31-33

on day 12 following the natriuresis caused by a diuretic. However, the pulmonary oedema increased again on day 16 (fig. 7) and this was attributed to IPPV and an increased intake of sodium (188 m.equiv) due to the blood transfusion. The oedema was less on day 19 and cleared by day 20. The persistent homogenous opacity on the right side (table VIII) was due to an effusion.

Case report The patient suffered multiple injuries with a haemopneumothorax, fractures of the second rib and pelvis, and there was tenderness and guarding in the abdomen. She was treated by intravenous infusions, oxygen from a MC mask and drainage of the pneumothorax. The blood showed hypercapnia (day 1) which was never explained. Mannitol was used to start urine formation and followed by intravenous feeding for 8 days. Progress was good until day 3 when chest pain made the cough ineffective. This was successfully treated by IPPV from a mouthpiece, and chest physiotherapy. On the evening of day 3 there was severe abdominal pain and shock due to bleeding from a tear in the liver, which was sutured. At the same time an elective tracheostomy was carried out because it was felt that the laparotomy would prevent successful conservative management of the respiratory failure. Controlled IPPV with deliberate hyperventilation (mean PaC0! 28 mm Hg, « = 9 ) was used for 5.5 days (treatment days 3-8) and assisted IPPV for 2 days. Weaning started on day 9. On day 11, IPPV was not used; when breathing 60 per cent oxygen respiration was rapid and shallow but became normal within the next 2 days. On day 15 a blood transfusion (2 pints over 6 hours) was given for anaemia. No antibiotics were given. On day 10 a small volume of blood-stainrd fluid was aspirated from the left pleural space and larger effusions were removed from the right chest on days 28 and 34. Recovery was complete. Sodium retention occurred on days 5-10 and 14-16, that is 4-6 days after stopping IPPV. Water retention occurred on days 8-9 (table IV). Natriuresis followed diuretic therapy on days 11—12 and occurred spontaneously on day 18 (fig. 3). Pulmonary oedema was observed on day 7 (fig. 5) and increased up to day 11 (fig. 6), when the oedema caused rapid shallow breathing. The oedema was less

FIG. 5 Chest radiograph on the sixth patient on day 7. Enlarged hila (+ +). Prominent vascular pattern.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

7

Pulmonary oedema

Sodium balance

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION

FIG. 7 Chest radiograph on the sixth patient on day 16. Enlarged hila ( + +). Increase in homogeneous opacity.

TABLE VIII

Radiological findings on the sixth patient. Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Day 8 & 9

Pneumothorax. Surgical emphysema. Bilateral homogeneous opacities, lower zones. Lung expanded. Other signs as for day 1. As for day 2. Surgical emphysema less. Other signs as for day 2. Increase in heart size. Other signs as for day 2. Further increase in heart size. Other signs as for day 2. Enlarged hila ( + + ) . Prominent vascular pattern. Further increase in heart size. As for day 7. DISCUSSION

Sodium retention during IPPV. We considered and dismissed the following causes of sodium retention. (i) Dehydration. None of the patients showed dehydration but three had moderate uraemia (table V).

Day 10

Vascular pattern less prominent. Other signs as for day 7. Day 11 Further increase in heart size. Bilateral homogeneous opacities, middle and lower zones. Day 12 Decrease in heart size, hila smaller (+). Reduced homogeneous opacities. Days 13-15 As for day 12. Day 16 Increase in homogeneous opacity on the right. Hila increased in size (+ +). Day 17 & 18 As for day 16. Hila smaller ( + ). Day 19 Other signs as for day 16. Day 20 Hila normal. Other signs as for day 16. (ii) Congestive cardiac failure. Only one patient (No. 7) had clinical signs of left ventricular failure and electrocardiographic evidence of heart disease. This patient showed sodium retention on the day after starting IPPV and also during convalescence. In the six other patients primary heart disease could not be incriminated as a cause of sodium retention or pulmonary oedema.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

FIG. 6 Chest radiograph on the sixth patient on day 11 (before diuretic). Enlarged hila ( + + ) . Bilateral homogeneous opacities, middle and lower zones.

467

BRITISH JOURNAL OF ANAESTHESIA

468 (iii) Acute intrinsic renal failure. Three of the patients had moderate uraemia but without serious oliguria of hyperkalaemia. None of our patients showed progressive uraemia and the sodium retention quickly responded to a diuretic. In patients 4 and 5 the uraemia cannot be explained but in patient No. 7 the uraemia was probably due to the reduced glomerular nitration rate of congestive cardiac failure.

(v) Hyper- and hypocapnia. Chronic hypercapnia displaces the carbon dioxide titration curve upwards and the increased reabsorption bicarbonate may retain excess sodium. Two of the patients had persistent hypercapnia late in their illness and this may have contributed to the sodium retention; both patients showed clinical oedema. Deliberate hyperventilation produced a respiratory alkalosis in five patients, but we do not know if this affected sodium metabolism.

Aetiology of pulmonary oedema during IPPV. The radiological signs of pulmonary oedema during IPPV have been reported in cases of chest injury, multiple injuries (Moore et al., 1969), fat embolism (Scott, Kemp and Robb-Smith, 1942) or following the inhalation of vomit. Pulmonary oedema is a rare complication of IPPV when the lungs are entirely normal, although Sladen, Laver

TABLE IX

Biochemical affects of artificial respiration. Results described by other authors. Authors and date

Species

Type of artificial apparatus

Results

Decrease in urine flow and urea Man PPB clearance. Diuresis Dog NPB Diuresis without change in excretion of NPB Man sodium or potassium or creatinine clearance. Diuresis increase in solute but fall in Love et al. (1957) Man Pulsatile PB in osmolality. Murdaugh, Sieker and Decrease in urine flow, free water Man PPB clearance, creatinine clearance and Manfredi (1959) sodium excretion. Increase in urine flow and free water NPB clearance. Decrease in urine flow, glomerular Baratz and Ingraham (1960) PPB Dog filtration rate and venal plasma flow No consistent change. NPB Decrease in urine Na/K ratio, increase Cox et al. (1963) PPR Man in aldosterone secretion. Decrease in urine flow. Tarak and Chaudhury (1965) PPR Rat Retention of water. Bushnell et al. (1966) IPPR Man Sladen, Laver and Pontoppidan IPPR Decrease in urine flow, hyponatraemia. Man Diuresis with ethacrynic acid. (1968) PPB, NPB, positive or negative pressure breathing. PPR, positive pressure respiration. Drury, Henry and Goodman (1947) Gauer et al. (1954) Sieker, Gauer and Henry (1954)

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

(iv) The metabolic response to injury. This causes negative balance of nitrogen and potassium and the positive balance of sodium. This metabolic pattern is largely prevented if a diet high in nitrogen and calories is started and continued into convalescence; our patients were routinely given such diets.

(vi) Steroid treatment. Large doses of hydrocortisone or prednisolone cause retention of sodium and water. Intensive steroid therapy was used in only one patient (No. 5) in whom it may have contributed to the positive balance of sodium. Our findings suggest that sodium retention invariably occurs when IPPV is used to treat seriously ill patients who have varied pulmonary pathology. The experiences of others in respiration units suggest that persistent sodium retention is an unlikely finding in patients undergoing long term IPPV, and whose lungs are normal. The mechanism of the sodium retention is unknown. Other authors have shown (table IX) that positive pressure breathing and IPPV directly cause retention of sodium and water and that the mechanisms are possibly hormonal.

PULMONARY OEDEMA ASSOCIATED WITH SODIUM RETENTION

Fluid and electrolyte therapy during IPPV. Following the demonstration of sodium retention during IPPV we have reduced the daily intake of sodium to about 60 m.equiv but emphasize that this step alone would not prevent sodium retention. Daily weighing of the patient, a record of the fluid intake and urine output, specific gravity or osmolality are necessary during IPPV, but cannot be used as substitutes for a sodium balance. When sodium retention is associated with the radiological signs of pulmonary oedema, a diuretic should be given promptly. On the other hand, when sodium retention occurs without pulmonary oedema, there is a choice of either restoring sodium balance by giving a diuretic, or of allowing the sodium retention to continue. ACKNOWLEDGEMENTS

P.M.G. was in receipt of a travel grant made to the University of Sydney by the New South Wales Joint Coal Board, and a personal grant from Prescot Rotary.

The laboratory studies were supported by grants to E.S.J. from the Research Committee of the United Liverpool Hospitals and the Asthma Research Council. The first, third and fifth patients were referred from hospitals outside our group. REFERENCES

Ashbaugh, D. G., Bigelow, D. B., Petty, T. L., and Levine, B. E. (1967). Acute respiratory distress in adults. Lancet, 2, 319. Avery, E. E., Morch, E. T., and Benson, D. W. (1956). Critically crushed chests. J. thorac. Surg., 32, 291. Barach, A. L. (1926). The effects of atmosphere rich in oxygen on normal rabbits with pulmonary tuberculosis. Amer. Rev. Tuberc, 13, 293. Baratz, R. A., and Ingraham, R. C. (1960). Renal hemodynamics and antidiuretic hormone release associated with volume regulation. Amer. J. Physiol., 198, 565 Bushnell, L. S.; Pontoppidan, H., Hedley-Whyte, J., and Bendixen, H. H. (1966). Efficiency of different types of ventilation in long-term respiratory care. Anesth. Analg. Curr. Res., 45, 696. Casdeman, B., and McNeely, B. U. (1967). Case records of Massachusetts General Hospital: Case 7-1967. New Engl. J. Med., 276, 401. Cederberg, A., Hellsten, S., and Miorner, G. (1965). Oxygen treatment and hyaline pulmonary membranes in adults. Ada path, microbiol. scand., 64, 450. Cox, J. R., Davies-Jones, A. B., Leonard, P. J., and Singer, B. (1963). The effect of positive pressure respiration on urinary aldosterone excretion. Clin. Sci., 24, 1. Drury, D. R., Henry, J. P., and Goodman, J. (1947). The effects of continuous pressure breathing on kidney function. J. clin. Invest., 26, 945. Finnegan, P., and Jones, E. S. (1969). Treatment of respiratory failure due to chronic lung disease by intermittent positive pressure ventilation. Brit. J. Anaesth., 41, 856. Gauer, O. H., Henry, J. P., Sieker, H. O., and Wendt, W. E. (1954). The effect of negative pressure breathing on urine flow. J. clin. Invest., 33, 287. Jones, E. S., and Peaston, M. J. T. (1966). Metabolic care during acute illnesses. Practitioner, 196, 271. Sechiari, G. P. (1963). Method of providing metabolic balance during intensive patient care. Lancet, 1, 19. Lancet (1964). A unit for intensive patient care. 1, 657, Linton, R. C , Walker, F. W., and Spoerel, W. E. (1965). Respiratory care in a general hospital: a five-year survey. Canad. Anaesth. Soc. J., 12, 450, Love, A. H. G., Roddie, R. A., Rosenweig, J., and Shanks, R. G. (1957). The effects of pressure changes in the inspired air on the renal excretion of water and electrolytes. Clin Sci., 16, 281. Moore, F. D., Lyons, J. H., Pierce, E. C , Morgan, P . A., Drinker, P. A., MacArthur, J. D., and Dammin, G. J. (1969). Post-traumatic Pulmonary Insufficiency, p. 158. London: Saunders. Murdaugh, H. V. jr., Sieker, H. O., and Manfredi, F . (1959). Effects of altered intrathoracic pressure on renal hemodynamics, electrolyte excretion and water clearance J. clin. Invest., 38, 834.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

and Pontoppidan (1968) reported such a case. Pulmonary oedema is rarely seen in patients undergoing long-term ventilation for neurological diseases. Clinical experience, together with animal experiments, strongly support the conclusion that IPPV with high concentrations of oxygen (70100 per cent) can cause pulmonary oedema which can progress to pulmonary fibroplasia. Our patients received inspired concentrations of oxygen in the range of 25-65 per cent, which are generally considered to be safe. What caused the pulmonary oedema seen in these patients ? We appreciate that the pulmonary oedema might be attributed solely to the acute respiratory failure (and left ventricular failure in one patient) caused by chest injury and so on. The correlations between sodium metabolim and the waxing and waning of the oedema strongly suggest that sodium retention was an important cause of pulmonary oedema in these patients. We believe that in three patients the correction of sodium retention by diuretics prevented either the development or progression of pulmonary oedema to cause serious effects on lung function. The oedema appeared to occur almost selectively in the lung, rather than in the limbs or trunk, but this finding requires confirmation by measurements of the body fluid compartments.

469

470

BRITISH JOURNAL OF ANAESTHESIA

OEDEME DU POUMON ASSOCIE A UNE RETENTION SODIQUE AU COURS D'UN TRAITEMENT PAR VENTILATION ARTIFICIELLE SOMMAIRE

On a eu recours a une ventilation intermittente hyperbare en vue du traitement de sept malades adultes atteints d'insuffisance respiratoire consecutive a un traumatisme du thorax, a une paralysie, a une infection pulmonaire ou a l'inhalation de vomissements. Sur ces sept malades, six ont ete gueris. Dans toute la mesure du possible, la tension de l'oxygene inspire a ete maintenue entre 200 et 300 mm Hg. Des examens du bilan metabolique ont ete effectu^s en liaison avec des radiographies thoraciques quotidiennes. Une retention sodique est survenue chez tous sept malades, son installation remontant chez quatre malades a quelques jours apres la mise en oeuvre de la ventilation artificielle intermittente hyperbare. Les cliches radiographiques de quatre malades comportaient des signes d'oedeme pulmonaire apparu au cours de la ventilation artificielle et la survenue de l'oedeme pulmonaire coincidait avec des periodes de retention sodique. Au cours de la ventilation artificielle, le recours & un diuretique a habituellement determine une natriurese et dans quatre cas, cette derniere s'est accompagnee d'une regression des symptomes d'oedeme pulmonaire. Les mecanismes physiologiques par Pintermediaire desquels la ventilation artificielle intermittente hyperbare determine une retention sodique et un oedeme du poumon, ne sont pas connus. II serait necessaire de recourir a I'administration de diuretiques au cours de la ventilation artificielle intermittente hyperbare, lorsqu'en

l'absence d'une deshydratation, le bilan sodique demeure positif pendant plus de 3 jours ou lorsque les radiographies thoraciques montrent la presence de signes d'oedeme pulmonaire. LUNGENoDEM UND NATRIUM-RETENTION WAHREND DER BEATMUNG ZUSAMMENFASSUNG

Es wurdensieben erwachsenen Patienten, die auf Grund einer Brustkorbverletzung, einer Lahmung, einer Lungeninfektion oder einer Aspiration von Erbrochenem an einem Versagen der Atmung litten, mit einer intermittierenden, positiven Druckventilation behandelt. Sechs dieser Patienten erholten sich. Die spannung des eingeatmeten Sauerstoffs wurde soweit moglich auf 200 bis 300 mm Hg gehalten. Taglich wurde das Stoffwechselgleichgewicht kontrolliert und die Lunge gerontgt. Eine Retention von Natrium war bei alien sieben Patienten festzustellen. Diese entwickelte sich bei vier Patienten wenige Tage nach Beginn der intermittierenden, positiven Drucktherapie (IPDV). Auf den Rontgenbildern von vier Patienten waren Anzeichen fur ein Lungenodem, das sich wahrend der IPDV entwickelte, zu sehen. Dieses Odem fiel mit den Perioden der Natriumretention zusammen. Wahrend der IPDVTherapie wurde durch eine Diurese gewohnlich eine Natriurese verursacht, was in vier Fallen eine Reduzierung des Lungenodems zur Folge hatte. Der physiologische Mechanismus, der fur die Entstehung einer Natriumretention und eines Lungenodems durch die IPDV-Therapie verantwortlich ist, ist unbekannt. Es sollten daher, falls keine Dehydratation vorliegt, Diuretika wahrend der IPDV-Therapie gegeben werden> wenn die Natriumbilanz mehr als drei Tage positiv ist oder Anzeichen eines Lungenodems auf dem Rontgenbild zu erkennen sind. EDEMA PULMONAR ASOCIADO CON RETENCION DE SODIO DURANTE EL TRATAMIENTO POR VENTILACION RESUMEN

Fue usada la ventilacion con presidn positiva intermitente para tratar a siete pacientes adultos con insuficiencia respiratoria debida a lesidn toracica, paralisis, infeccion pulrnonar o inhalacion de v6mito. Seis de estos siete pacientes se restablecieron. La tension del oxigeno inspirado fue mantenida entre 200 a 300 mm Hg cuando posible. Los estudios del balance metabdlico fueron correlacionados con radiografias diarias del torax. Hubo retenci6n de sodio en los siete pacientes, que en cuatro pacientes ocurri<5 a los pocos dias de comenzar la IPPV. Las radiografias de cuatro pacientes mostraron signos de edema pulmonar desarrollandose durante la IPPV, y el desarrollo de edema pulmonar estaba correlacionado con los periodos de retenci6n de sodio. Durante la IPPV un diuretico generalmente causaba una natriuresis, y en cuatro casos esto fue seguido por una reducci<5n de los signos de edema pulmonar. Los mecanismos fisiologicos por los cuales la IPPV causo retenci6n de sodio y edema pulmonar son desconocidos. Durante la IPPV se debe administrar diur£ticos ciiando, no habiendo deshidrataci6n, el balance de sodio es positivo durante mas de 3 dias o cuando la radiografia del tdrax muestra signos de edema pulmonar.

Downloaded from http://bja.oxfordjournals.org/ at Simon Fraser University on May 31, 2015

Peaston, M. J. T. (1966). Design of an intravenous diet of amino-acids and fat suitable for intensive patient care. Brit. med. J., 2, 338. (1967). Maintenance of metabolism during intensive patient care. Postgrad, med. J., 43, 317. Scott, J. C , Kemp, F. H , and Robb-Smith, A. H. T. (1942). Pulmonary fat embolism. Lancet, 1, 228. Sieker, H. O., Gauer, O. H., and Henry, J. P. (1954). The effect of continuous negative pressure breathing on water and electrolyte excretion by the human kidney. J. clin. Invest., 33, 572. Sladen, A., Laver, M. B., and Pontoppidan, H. (1968). Pulmonary complications and water retention in prolonged mechanical ventilation. New Engl. J. Med., 279, 448. Smith, A. C. (1967). Discussion to the paper by O. P. Norlander and I. Norden. Postgrad, med. J., 43, 277. Smith, J. L. (1899). The pathological effects due to increase of oxygen tension in the air breathed. J. Physiol. (.Lond.), 24, 19. Sykes, M. K. (1963). Venous pressure as a clinical indication of adequacy of transfusion. Ann. roy. Coll. Surg. Engl, 33, 185. Tarak, T. K., and Chaudhury, R. R. (1965). The mechanism of positive pressure respiration induced antidiuresis in the rat. Clin. Sci., 28, 407. Thompson, G. S., and Jones, E. S. (1965). Errors in the measurement of serum electrolytes. J. clin. Path., 18, 443.