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Sputum Viscosity and Postoperative Pulmonary Atelectasis
Sputum Viscosity and Postoperative Pulmonary Atelectasis* GERALD BLANSHARD, M.D. (Cantab.) , M.R.C.P.** London, England
The relationship between changes in the viscosity of sputum and the development of pulmonary atelectasis has been diacussed.>" The fibers found in sputum which appear to be responsible for the viscosity are TABLE I VISCOSITY OF SPUTUM BEFORE AND AFTER OPERATION UNDER GENERAL ANESTHESIA
Case Number Number of Days
-7 -6
1
2
3
4
5
6
105 305 206 73 173 221 67
323
-3
305 160
346 309
-2
320 80 235 160
-5 -4
-1
7
342 570 453 789
54 34 18 37
Day of Operation under General Anesthesia 727 . 1,087 1,007 327 1,440 1,080 571 204 317 973
187 151
58 370
24
19
111
193 33
132 20
119 84
+1
948 423
+2
250 184
767 341
716 476
266 179
752 606
51 12
+3
82 94
346 535
465 450 259 81
71 85 75 28 59 67 61 85 45
291 514
109 44
382
55 51 109 45 62 57 28
+4 +0
503 460 590
8 98
+6
8 67
+7
7
The figures are the degrees of deflection on the viscometer produced by sputum expectorated through the day and overnight-more viscous sputum producing greater deflection, according to the method.· *From the Department of Medicine, Middlesex Hospital. ··Senior Medical Registrar. This work forms part of a University of Cambridge M.D. thesis.
75
FIGURE IA
FIGURE 1B
FIGURE IC
Figure 1A: Sputum viscosity measurements before and after operation showing the increase at the time of operation and the development of postoperative pulmonary atelectasis is illustrated in Figures IB and Ie. ·Figure 18: Preoperative chest x-rayon Case 1. Figure 1C : Postoperative chest x-rayon Case, showing atelectasis of the left lower lobe.
f i
I~
·-
....
, -,'. 1
...
FIGURE 2A
1.16
,. FIGURE 2B
FIGURE 2C
Figure 2A : Sputum viscosity measurements before and after operation, showing the increase at the time of operation. The development of postoperative pulmonary atelectasis is illustrated in Figures 2B and 2C. Figure 2B: Preoperative chest x-rayon Case 2. F igure 2C : Postoperative chest x-rayon Case 2 snowing atelectasis in the right lower lobe.
78
GERALD BLANSHARD
.ranuary, 1960
TABLE II RELATING THE SIOZE AND DURATION OF THE INCREASE IN VISCOSITY OF SPUTUM TO PREMEDICAMENTS AND ANESTHETI'C AGENTS AT OPERATION
1
2
S
•
5
6
5x
2x
7x
6x
3x
3x
36
60
89
66
22
22
Case Number: Basal viscosity increased by: Duration of viscosity rise . in hours: Premedieation Omnopon (mgm.) Scopolamine (mgm.)
0.4
Pethidine (mgm.)
250
Morphine (mgm.)
32
0.4
24 11
11
0.6
0.4
250
200
0••
0.2
100
16
Atropine (mgm.) Anesthetfe Oxygen Nitrous oxide
0.6
+ +
+ +
Ether Cyclopropane Thiopentone Tubarine Trichlorethylene Pethidine
7
+ +
+ +
+ +
+
Succinyl choline
+ + +
+ + +
+
+
+ +
+ + +
+
+
+ +
+
mucoprotein and deoxyribonucleoprotein; the former is formed in the goblet cells of the bronchial mucosa and the mucous secreting submucosal glands, whilst the latter is formed from the nuclear deoxyribonucleic acid of degenerating pus cells. This work was .an attempt to measure changes in viscosity during the operative period and to investigate some of the infiuencing factors. Method The patients studied were in hospital for elective surgery. They were suffering from chronic bronchitis which was in a stable phase--neither developing nor recovering from an acute infection, nor were they having TABLE III THE EFFECT OF ATROPINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer) Before atropine
31 19
372 452
204 285
1 mgm. s.c, After atropine
15
55 72
236 283
92 45
286 587
0.5 mgm. 138 325
119 193
167
468 427
SPUTUM VISCOSITY
Vol. XXXVII
79
TABLE IV THE EFFECT OF PETHI'DINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer) Daily measurements of viscosity before pethidine 174 270 227 442 490 269 254 After pethidine
254 295 303 281 342
52 32 20 30
Pethidine 100 mgm. intramuscularly 622 297 369
525 481 290
52 162 20 125 38 249 35 180 219 275 212 50 mgm. intramuscularly
66 124 58
455 37
changing medicinal therapy. They were expectorating a constant amount of mucoid sputum and measurements of the viscosity were made using the technique described elsewhere," The effect of operating under general anesthesia was investigated in seven instances; one patient had two operations. The effect of atropine was investigated on six occasions, subcutaneous injection of I mgm. in two and 0.5 mgm, in four instances. Pethidine, 100 mgm. intramuscularly in three patients and 50 mgm, in another patient was investigated. Codeine phosphate, 22 mgm. intramuscularly in three and 65 mgm. orally in another patient was tried. Results Measurements of the viscosity of the sputum expectorated by these patients before and after operation are shown in Table I; details of premedication and anesthetic agents used are shown in Table II. Figures IA and 2A show the increase in viscosity in two patients who had the misfortune to develop postoperative pulmonary atelectasis illustrated in Figures IB and IC in the first patient, and in Figures 2B and 2C jn the second. The effects of atropine, pethidine and codeine are shown in Tables III, IV and V respectively. ' ·TABLE V THE EFFECT OF CODEINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer)
Daily measurements of viscosity before codeine
31 149 49 120
166 460 549
180 51 112
22 mgm. i.m, 766 120 440
After codeine
190 203 543 600 1,065 593 175
81 52 42 65 mgm, orally 255 164 126
80
GERALD BLANSHARD
January. 1960
Discussion The efficient expectoration of sputum depends on ciliary activity, air flow during quiet respiration or coughing and bronchial movement; ciliary activity is impaired by deviations of viscosity from the normal ideal range.' The viscous nature of sputum is mainly due to the fibers of mucoprotein and deoxyribonucleoprotein which it contains. Increasing the viscosity impairs sputum expulsion and the consequent sputum retention predisposes to the development of bronchial occlusion and atelectasis. The various factors affecting the viscosity at t he time of operation have been discussed in detail"; the more important are the state of body hydration, drugs-used for premedication, anesthesia or postoperative pain-and the depth and duration of anesthesia. The development of postoperative pulmonary atelectasis in Cases 1 and 2 coincided with the maximum increase in sputum viscosity; the preoperative measurements in Case 1 illustrate the diurnal variation, overnight sputum being more viscous than that produced during the day. Correlating the extent and duration of the increase in viscosity with drugs used for premedication, Cases 1, 3 and 4 received more morphine and pethidine than the other cases (Table II) . Examination of the results from the experiments with atropine reveals no significant increase in viscosity ; atropine abolishes the neurogenically controlled submucosal gland secretion, effecting a quantitative rather than a qualitative change in the bronchial secretion. Goblet cell secretion, and the vehicle formed by transudation from the pulmonary vascular bed, are presumably not influenced by atropine. The increased viscosity following pethidine administration suggests that this drug should be used with caution in patients with chronic respiratory disease. After the administration of codeine phosphate, the apparent increase in viscosity substantiates the observations of Basch' and Folken." Hillis," investigating the effect of drugs on the cough reflex, found codeine without effect in contradistinction to morphine, diamorphine and amidone which were powerful suppressives and will consequently produce sputum retention. SUMMARY Change in the viscosity of sputum expectorated by patients suffering from chronic bronchitis in a stable phase, was measured. Operation under general anesthesia produced an increase in viscosity which, in two patients, was associated with the development of postoperative pulmonary atelectasis. Atropine produced no apparent increase in viscosity while there was some increase after pethidine and codeine.
Acknowledgment: The author gratefully acknowledges Prof. A. Kekwick for his help and the consultants of .the Middlesex Hospital for permission to study patients under their care. RESUMEN Se ha medido el cambio en la viscosidad del esputo expectorado por enfermos de bronquitie cronice en fase estable. La operacion bajo anestesia general produjo un aumento de la viscosidad que en dos enfermos fue asociado con la presencia de atelectasia pulmonar postoperatoria. La tropina no produjo aparente aumento de la viscosidad en tanto que silo hubo despues de pethidina y de la codeina, RESUME Les modifications de la viscosite de l'expectoration des malades atteints de bronchite chronique furent mesurees alors que ces malades etaient en periode stable. Une intervention sous anesthesie generale produisit une augmentation de la visco site qui, chez deux malades, entraina une atelectasie pulmonaire post-operatoire. L'atropine ne produisit aucune augmentation apparente de la viscosite tandis qu'il y eut une augmentation apres l'administration de pethidine et de codeine. ZUSAMMENFASSUNGEN Es wurden die Veriinderungen in der Viskositiit von Sputum gemessen bei Kranken mit chronischer Bronchitis in einer stabilen Phase. Operationen unter Vollnarkose filhrten zu einem Anstieg in der Viskositiit; diese war bei 2 Patienten vehkniipft mit dem Auftreten postoperativer pulmonaler Atelektasen. Atropin bewirkte keine augenfiillige Zunahme der Viskositiit; jedoch ergab sich eine gewisse Zunahme nach Pethidin oder Codein. REFERENCES 1 Elliott, T. R. and Dingley, L. A.: " Ma ssive Collapse of the Lungs Following Abdominal Operations," Lancet, 1 :1305, 1914. 2 Lee, W. E., Tucker, G., Ravdin, I. S. and Pendergrass, E. P.: " E xper imental Atelectasis," Arch. Burg., 18 :242, 1929. 3 Coryllos, P. N. and Birnbaum, G. L. : "Syndrome of Pneumococcic Bronchial Ob· struction," Arch. Int. Med., 51 :290, 1933.
Vol.
xxxvn
SPUTUM VISCOSITY
81
4 Brock, R. C.: "Post-Operative Chest Complications," Guy's Hosp, Rep., 86:191, 1936. 5 Palmer, K. N. V. and Sellick, B. A. : "The Prevention of Postoperative Pulmonary Atelectasis," Lancet, 1 :164, 1963. 6 Blanshard, G.: "The Viscometry of Sputum," Arch. Middlesex Hoep., 6:222, 1966. 7 Negus, V. E.: "The Action of Cilia and the Effect of Drugs on Their Activity," J. Laryng., 49 :671, 1934. 8 Blanshard, G. (in press) . 9 Basch, F . P., Holinger, P. and Poncher, H. G.: "Physical and Chemical Properties of Sputum," 'A m . J. Dis. cuu; 62 :981 and 62 :1149, 1941. 10 Folken, F. G.: "Acute Laryngotracheobronchitis," Minnesota Med., 36 :336, 1952. 11 Hillis, B. R.: "The Assessment of Cough Suppressing Drugs," Lancet, 1 :1230, 1962.
The relationship between changes in the viscosity of sputum and the development of pulmonary atelectasis has been diacussed.>" The fibers found in sputum which appear to be responsible for the viscosity are TABLE I VISCOSITY OF SPUTUM BEFORE AND AFTER OPERATION UNDER GENERAL ANESTHESIA
Case Number Number of Days
-7 -6
1
2
3
4
5
6
105 305 206 73 173 221 67
323
-3
305 160
346 309
-2
320 80 235 160
-5 -4
-1
7
342 570 453 789
54 34 18 37
Day of Operation under General Anesthesia 727 . 1,087 1,007 327 1,440 1,080 571 204 317 973
187 151
58 370
24
19
111
193 33
132 20
119 84
+1
948 423
+2
250 184
767 341
716 476
266 179
752 606
51 12
+3
82 94
346 535
465 450 259 81
71 85 75 28 59 67 61 85 45
291 514
109 44
382
55 51 109 45 62 57 28
+4 +0
503 460 590
8 98
+6
8 67
+7
7
The figures are the degrees of deflection on the viscometer produced by sputum expectorated through the day and overnight-more viscous sputum producing greater deflection, according to the method.· *From the Department of Medicine, Middlesex Hospital. ··Senior Medical Registrar. This work forms part of a University of Cambridge M.D. thesis.
75
FIGURE IA
FIGURE 1B
FIGURE IC
Figure 1A: Sputum viscosity measurements before and after operation showing the increase at the time of operation and the development of postoperative pulmonary atelectasis is illustrated in Figures IB and Ie. ·Figure 18: Preoperative chest x-rayon Case 1. Figure 1C : Postoperative chest x-rayon Case, showing atelectasis of the left lower lobe.
f i
I~
·-
....
, -,'. 1
...
FIGURE 2A
1.16
,. FIGURE 2B
FIGURE 2C
Figure 2A : Sputum viscosity measurements before and after operation, showing the increase at the time of operation. The development of postoperative pulmonary atelectasis is illustrated in Figures 2B and 2C. Figure 2B: Preoperative chest x-rayon Case 2. F igure 2C : Postoperative chest x-rayon Case 2 snowing atelectasis in the right lower lobe.
78
GERALD BLANSHARD
.ranuary, 1960
TABLE II RELATING THE SIOZE AND DURATION OF THE INCREASE IN VISCOSITY OF SPUTUM TO PREMEDICAMENTS AND ANESTHETI'C AGENTS AT OPERATION
1
2
S
•
5
6
5x
2x
7x
6x
3x
3x
36
60
89
66
22
22
Case Number: Basal viscosity increased by: Duration of viscosity rise . in hours: Premedieation Omnopon (mgm.) Scopolamine (mgm.)
0.4
Pethidine (mgm.)
250
Morphine (mgm.)
32
0.4
24 11
11
0.6
0.4
250
200
0••
0.2
100
16
Atropine (mgm.) Anesthetfe Oxygen Nitrous oxide
0.6
+ +
+ +
Ether Cyclopropane Thiopentone Tubarine Trichlorethylene Pethidine
7
+ +
+ +
+ +
+
Succinyl choline
+ + +
+ + +
+
+
+ +
+ + +
+
+
+ +
+
mucoprotein and deoxyribonucleoprotein; the former is formed in the goblet cells of the bronchial mucosa and the mucous secreting submucosal glands, whilst the latter is formed from the nuclear deoxyribonucleic acid of degenerating pus cells. This work was .an attempt to measure changes in viscosity during the operative period and to investigate some of the infiuencing factors. Method The patients studied were in hospital for elective surgery. They were suffering from chronic bronchitis which was in a stable phase--neither developing nor recovering from an acute infection, nor were they having TABLE III THE EFFECT OF ATROPINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer) Before atropine
31 19
372 452
204 285
1 mgm. s.c, After atropine
15
55 72
236 283
92 45
286 587
0.5 mgm. 138 325
119 193
167
468 427
SPUTUM VISCOSITY
Vol. XXXVII
79
TABLE IV THE EFFECT OF PETHI'DINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer) Daily measurements of viscosity before pethidine 174 270 227 442 490 269 254 After pethidine
254 295 303 281 342
52 32 20 30
Pethidine 100 mgm. intramuscularly 622 297 369
525 481 290
52 162 20 125 38 249 35 180 219 275 212 50 mgm. intramuscularly
66 124 58
455 37
changing medicinal therapy. They were expectorating a constant amount of mucoid sputum and measurements of the viscosity were made using the technique described elsewhere," The effect of operating under general anesthesia was investigated in seven instances; one patient had two operations. The effect of atropine was investigated on six occasions, subcutaneous injection of I mgm. in two and 0.5 mgm, in four instances. Pethidine, 100 mgm. intramuscularly in three patients and 50 mgm, in another patient was investigated. Codeine phosphate, 22 mgm. intramuscularly in three and 65 mgm. orally in another patient was tried. Results Measurements of the viscosity of the sputum expectorated by these patients before and after operation are shown in Table I; details of premedication and anesthetic agents used are shown in Table II. Figures IA and 2A show the increase in viscosity in two patients who had the misfortune to develop postoperative pulmonary atelectasis illustrated in Figures IB and IC in the first patient, and in Figures 2B and 2C jn the second. The effects of atropine, pethidine and codeine are shown in Tables III, IV and V respectively. ' ·TABLE V THE EFFECT OF CODEINE ON THE VISCOSITY OF SPUTUM (Degrees of Deflection on the Viscometer)
Daily measurements of viscosity before codeine
31 149 49 120
166 460 549
180 51 112
22 mgm. i.m, 766 120 440
After codeine
190 203 543 600 1,065 593 175
81 52 42 65 mgm, orally 255 164 126
80
GERALD BLANSHARD
January. 1960
Discussion The efficient expectoration of sputum depends on ciliary activity, air flow during quiet respiration or coughing and bronchial movement; ciliary activity is impaired by deviations of viscosity from the normal ideal range.' The viscous nature of sputum is mainly due to the fibers of mucoprotein and deoxyribonucleoprotein which it contains. Increasing the viscosity impairs sputum expulsion and the consequent sputum retention predisposes to the development of bronchial occlusion and atelectasis. The various factors affecting the viscosity at t he time of operation have been discussed in detail"; the more important are the state of body hydration, drugs-used for premedication, anesthesia or postoperative pain-and the depth and duration of anesthesia. The development of postoperative pulmonary atelectasis in Cases 1 and 2 coincided with the maximum increase in sputum viscosity; the preoperative measurements in Case 1 illustrate the diurnal variation, overnight sputum being more viscous than that produced during the day. Correlating the extent and duration of the increase in viscosity with drugs used for premedication, Cases 1, 3 and 4 received more morphine and pethidine than the other cases (Table II) . Examination of the results from the experiments with atropine reveals no significant increase in viscosity ; atropine abolishes the neurogenically controlled submucosal gland secretion, effecting a quantitative rather than a qualitative change in the bronchial secretion. Goblet cell secretion, and the vehicle formed by transudation from the pulmonary vascular bed, are presumably not influenced by atropine. The increased viscosity following pethidine administration suggests that this drug should be used with caution in patients with chronic respiratory disease. After the administration of codeine phosphate, the apparent increase in viscosity substantiates the observations of Basch' and Folken." Hillis," investigating the effect of drugs on the cough reflex, found codeine without effect in contradistinction to morphine, diamorphine and amidone which were powerful suppressives and will consequently produce sputum retention. SUMMARY Change in the viscosity of sputum expectorated by patients suffering from chronic bronchitis in a stable phase, was measured. Operation under general anesthesia produced an increase in viscosity which, in two patients, was associated with the development of postoperative pulmonary atelectasis. Atropine produced no apparent increase in viscosity while there was some increase after pethidine and codeine.
Acknowledgment: The author gratefully acknowledges Prof. A. Kekwick for his help and the consultants of .the Middlesex Hospital for permission to study patients under their care. RESUMEN Se ha medido el cambio en la viscosidad del esputo expectorado por enfermos de bronquitie cronice en fase estable. La operacion bajo anestesia general produjo un aumento de la viscosidad que en dos enfermos fue asociado con la presencia de atelectasia pulmonar postoperatoria. La tropina no produjo aparente aumento de la viscosidad en tanto que silo hubo despues de pethidina y de la codeina, RESUME Les modifications de la viscosite de l'expectoration des malades atteints de bronchite chronique furent mesurees alors que ces malades etaient en periode stable. Une intervention sous anesthesie generale produisit une augmentation de la visco site qui, chez deux malades, entraina une atelectasie pulmonaire post-operatoire. L'atropine ne produisit aucune augmentation apparente de la viscosite tandis qu'il y eut une augmentation apres l'administration de pethidine et de codeine. ZUSAMMENFASSUNGEN Es wurden die Veriinderungen in der Viskositiit von Sputum gemessen bei Kranken mit chronischer Bronchitis in einer stabilen Phase. Operationen unter Vollnarkose filhrten zu einem Anstieg in der Viskositiit; diese war bei 2 Patienten vehkniipft mit dem Auftreten postoperativer pulmonaler Atelektasen. Atropin bewirkte keine augenfiillige Zunahme der Viskositiit; jedoch ergab sich eine gewisse Zunahme nach Pethidin oder Codein. REFERENCES 1 Elliott, T. R. and Dingley, L. A.: " Ma ssive Collapse of the Lungs Following Abdominal Operations," Lancet, 1 :1305, 1914. 2 Lee, W. E., Tucker, G., Ravdin, I. S. and Pendergrass, E. P.: " E xper imental Atelectasis," Arch. Burg., 18 :242, 1929. 3 Coryllos, P. N. and Birnbaum, G. L. : "Syndrome of Pneumococcic Bronchial Ob· struction," Arch. Int. Med., 51 :290, 1933.
Vol.
xxxvn
SPUTUM VISCOSITY
81
4 Brock, R. C.: "Post-Operative Chest Complications," Guy's Hosp, Rep., 86:191, 1936. 5 Palmer, K. N. V. and Sellick, B. A. : "The Prevention of Postoperative Pulmonary Atelectasis," Lancet, 1 :164, 1963. 6 Blanshard, G.: "The Viscometry of Sputum," Arch. Middlesex Hoep., 6:222, 1966. 7 Negus, V. E.: "The Action of Cilia and the Effect of Drugs on Their Activity," J. Laryng., 49 :671, 1934. 8 Blanshard, G. (in press) . 9 Basch, F . P., Holinger, P. and Poncher, H. G.: "Physical and Chemical Properties of Sputum," 'A m . J. Dis. cuu; 62 :981 and 62 :1149, 1941. 10 Folken, F. G.: "Acute Laryngotracheobronchitis," Minnesota Med., 36 :336, 1952. 11 Hillis, B. R.: "The Assessment of Cough Suppressing Drugs," Lancet, 1 :1230, 1962.