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Experimental evaluation of the “gastric barrier” in CSF shunt infections
JOURNAL
0F
SURGICAL
RESEARCH
Experimental
16,
541645
(1974)
Evaluation
of the “Gastric
Shunt ROBERT
G. SELKER,
M.D.,* AND
DAVID
SIDNEY
BAHNSON, K.
From the Departments of Surgery and Medicine, University of Pittsburgh School of Medicine and the Montefiore Hospital, Pittsburgh, Pa. *Author’s Address: Dr. Robert G. Selker, Montefiore Hospital, 3459 Fifth Avenue, Pittsburgh, Pa. 15213. Submitted for publication January 19, 1974.
WOLFSON,
M.D.,
CARL
JR.,
M.D.
A. NORDEN,
M.D.,
staphylococcus, pseudomonas, serratia, E. Coli and infrequently aerobacter. The treatment currently employed involves intraventricular and systemic antibiotics with total removal of the shunt and/or externalization of the system for decompression and drainage purposes while treatment is being effected. Even then, many return reinfected. As a matter of fact, a large percentage of asymptomatic children undergoing elective revision (Ventriculo-atria1 shunts) will show positive cultures of cerebrospinal fluid (CSF) and of the catheter tip [3]. In the course of ones practice, most every neurosurgeon has noted the fact that externalization of the shunt with drainage into an outside reservoir (so called 5th ventricle) will render the child afebrile, bright, and an eager eater [ll]. It seems apparent that children can co-exist with an infected system without continuous antibiotic therapy as long as external drainage is continued. This has been confirmed in older children permitting their return to school and normal activity. Their infection could not be cleared sufficiently to allow implantation either into the vascular system or into the peritoneal cavity [S]. Thus, the experience of others corroborates our experience where fever, positive blood cultures, lethargy, and vomiting secondary to an infected shunt system can be reversed and maintained by instituting external drainage. Should the CSF not become sterile with repeated efforts, it seems reasonable to assume that if drainage were instituted into a body organ system and there
541 @ 1974 by Academic Press, Inc. of reproduction in anyjform reserved.
in CSF
Infections
THE CONCEPT OF A “GASTRIC BARRIER” to ingested organisms can be traced as far back as the turn of the century when it was described in association with bacterial dysenteries [7, 6, I]. The exact makeup and character of the barrier was, at the time, the object of a great deal of experimental effort and speculation. Secreted mucus, mucus membrane of the small intestine, type of food and its preparation, pepsin, bile, and lysozyme were all considered and soon abandoned [lo, 1, 21. As described by Giannella et al. in their review of the subject [4], it remained for others to show that patients with reduced or absent gastric acid secretions were more susceptible to bacterial dysenteries. Their repeated work with the bacteriocidal activity of normal and achlorhydric gastric juice established again the currently accepted concept that the “gastric barrier” is, in fact, the pH level of gastric secretion. Further, that a pH of less than 4 will kill 99% of most bacteria within a 30-min period of exposure, with other constituents of gastric juice contributing little if any detectable effect [5]. One of the major disadvantages of current shunt systems is the frequency with which they become infected. The common organisms include a coagulase negative
Copyright All rights
Barrier”
542
JOURNAL
OF SUHGICAL
RESEARCH,
voL.
16, x0. 5, nfAY 1974
Table 1. Changes in Gastric pH with Feeding Time
Average
High
Low
Standard deviation
Standard error
2.32 4.78 3.62 2, -50 2.08
3.6 6.4 4.8 4 3
1.4 2. 8 2. 4 1.5 1 5
..57 1.00 .78 .86 .44
,170 31.5 ,246 .273 ,140
Fasting 15 min post feeding SO min post feeding 60 min post feeding 120 min post feeding
2.8
prolonged external rendered harmless, drainage would be avoided. Such a site would be the gastric fundus, where a protective effect to colonization by the “gastric barrier” exists. In order to assess the potential use of this ‘Lbarrier” in infected shunts, several questions became immediately evident. A. What is the normal fasting pH of the infant and/or child? What is the buffering effect of normal milk and/or formula feeding? B. What is the effect of pH on the common shunt bacteria and the necessary duration of exposure to render them nonviable? C. At what concentration of bacteria can the ‘(gastric barrier” be overcome? D. Can feedings be supplemented by low pH fluids to achieve the critical level necessary to maintain the gastric barrier? To answer these questions the following experiments were undertaken. EXPERIMENTAL DATA RESULTS
AND
I. Normal Fasting pH of Infants and Children. Buffer Effect of Milk or Formula. Ten patients ranging in ages from 2 months to 9 yr were subjected to nasogastric intubation. Attempts were made to be certain of its position within the gastric fundus. Samples of gastric juice were analyzed for pH values in the fasting state, during natural sleep and anesthesia as well as 15, 30, 60, and 120 min after feeding. The pH of Enfamil@, Prosobee@, and milk were determined and found to be 6.4, 6.9, and 6.5 respectively.
The results of gastric pH analysis revcaled the following average values in infants being fed milk, Enfamil, or Prosobee (Mead Johnson). Fasting 15 min 30 min 60 min 120 min
state post post post post
feeding feeding feeding feeding
2.3 4.78 3.62 2.50 2.08
Values during natural sleep generally agreed with the fasting values, but time of sleep came most after 30 min of feeding, making it difficult to determine it as a separate category. Determinations during anesthesia range from 2-6.5 without a reasonable cluster of values. In general, it would appear to elevate the pH values, indicating a lesser acid concentration. From this data, it would appear quite evident that the feedings, especially milk, Enfamil@ and Prosobee@ (comparable pHs) have considerable buffering effect on the pH fasting values Table 1. pH values in the one older child with a normal house diet were essentially the same for the fasting sample but varied considerably with the menu of the day, ice cream and milk intake as well as with carbonated beverages. II. Effect of pH on Common Shunt Bacteria and the Necessary Ilura tion of Exposure. To determine the effect of pH on a common shunt contaminants, an elaborate experimental system utilizing staphylococcus albus and pseudomonas aeroginosa was undertaken in the following manner. a. The hospital laboratory provided an overnight growth of staphylococcus albus
SELKER
ET
AL.:
EVALUATION
and pseudomonas in trypticase soy broth, known to be in a stationary growth phase and which, on subsequent plating and colony count, was found to contain 10” colonies/cc. b. One cc aliquot of overnight stable growth phase solution (10” bacteria/cc) was added to 9 cc of buffered trypticase soy broth with pH values of 2, 3, 4 and 5. Stock buffer solutions were prepared using Coleman Certified Buffer Tablets (Distributed by The Perkin-Elmer Corp., Rlaywood, Ill.), a preparation to which no preservative is added (most stock pH solutions contain formalin). c. Each buffered pH solution containing the added bacteria was then sampled at 0, 15, 30, 60, and 120 min of exposure to the solution by removing a 1 cc aliquot, serially diluting this aliquot in trypticase soy broth and placing these aliquots in sterile petri dishes overlayed with sterile trypticase soy agar. d. All petri dishes were incubated for 24 hr at 37°C at which time colony counts were carefully made. Results. Results are expressed as a function of time and pH. Colony counts are expressed as absolute numbers or with the notation “too numerous to count” (TNTC) (Table 2). All pH solutions at 0 min of exposure revealed unhibited growth. At I5 min of exposure it became evident that very few colonies survived in solutions of less than pH 3 and were uninhibited in growth at pH over 4. All samples allowed 30 min exposure to solutions of pH 3 or less, revealed no
OF
THE
“GASTRIC
543
BARRIER”
growth following 24 hr of incubation It seems evident that a critical lethal pH existed somewhere between a pH 3 and pH 4 for bacteria exposed 15 min or more to the solution. Additional experiments lead us to believe this to be between 3.5 and 3,.&. Although the results graphically portrayed are for staphyloccus albus and pseudomonas almost identical values were obtained with overnight inoculums of serratia and E. Coli. III. Can the “Gastric Barrier” be Overcome? If so, at What Concentration? In order to determine the effect of large concentrations of bacteria upon the gastric barrier and to test the hypothysis in vivo, a primate model was established. The fasting gastric pH of the stumptailed macaques has previously been reported and this information was utilized in consideration of a primate model [9]. Although a formal gastric analysis was not performed in our animals, random fasting samples of gastric juice revealed comparable values. Two unstandard laboratory baboons selected (papio anubis) were subjected to surgery wherein a red rubber tube was securely placed in the fundus portion of the stomach. A subcutaneous tunnel was then created through the anterior chest wall, and continued laterally and posteriorly as well as superiorly to emerge over the occiput of the animal. Having been previously trained to sit for days in a special laboratory training chair, the operated monkeys were allowed to again stabilize and obtain a basal resting state with a normal gastric
Table 2. Results of Colony Counts of Staphylococcus and Pseudomonas using an Undiluted Overnight Culture Exposure time 0 15 30 60 120
min min min min min
B TNTC-too
numerous
PHI
PH
TNT0 60 0 0 0
TNTC 81 0 0 0
to count.
3
pH 3.5 TNTC 90 0 0 0
pH4
pH5
TNTC TNTC TNTC TNTC TNTC
TNTC TNTC TNTC TNTC TNTC
544
JOURNAL
OF
SURGICAL
RESEARCH,
VOL.
16,
NO.
t$
MAY
1974
fluids of 2, 3, 4, and 5. One cc of standard (109 overnight growth phase bacteria bacteria/cc) was diluted in 9 cc of Coca Cola and exposed for 0, 15, 30, 60, and 120 min. One cc aliquots of each time period were then placed in sterile petri dishes overlayed with trypicase soy agar and incubated for 24 hr at 37°C. Colony counts were performed as with original pH ohs- 15) solutions. 120 30 60 Tlme in minutes Results. No growth occurred after 15 min Fig. 1. Effect of coca cola (pH 2.2) on a 1 cc of exposure of the bacteria to Coca Cola. aliquot of overnight culture of stnph albus or Uninhibited growth was noted at 0 min and pseudomonas. similar experiments with ginger ale (pH 2.7) revealed similar results (Fig. 1). acid content uninfluenced by anesthesia or sedation. When sufficiently acclimated to the chair and tube, serial control stool cultures were obtained by rectal swab on three consecutive days. Utilizing a laboratory strain of pigmented “red” serratia in stable congrowth phase, solutions containing centrations between 1 and 50 million bacteria/cc were infused via the implanted tube at the rate of 0.5 cc/min. for 24 hr. Twenty-four-hr periods of no infusion were permitted to elapse between each concentration increase of 10 million bacteria. Serial rectal swabs were performed on a daily basis. Results. Throughout the entire experiment, no evidence of pigmented serratia ever appeared in the stool cultures to indicate a ‘(break” in the animal ‘[gastric barrier.” Feedings throughout this time consisted of standard Rockland Primate Stars, supplemented by apples. At no time was the animal given milk or any buffering substance as would normally occur in an infant.
DISCUSSIOX
The gastric barrier as described, has, by virtue of its pH, a protective effect against ingested bacteria. From a clinical point of view its effect in bacterial dysenteries is well documented in the literature. Its utilization, with persistent CSF shunt infections seems clearly quite reasonable. The average resting pH in an infant of approximately 2.6 is well below our established critical level of 3.5-3.8. During times of feeding the buffering effect of milk or Enfamil is dramatic, even though the greatest outpouring of gastric acid would be expected at that time. The experimental finding of t’he effectiveness of the pH of Coca Cola is surprising and pleasing in view of the uniform acceptability of this beverage. Although almost equal volumes of milk and Coke (Coca Cola Co.) are required to achieve a pH of less than 4 in vitro, no account has been made for gastric acid secretion in vivo during feeding. Confronted with a specie difference and an inherently lower gastric pH in baboons, the finding of gastric barrier protection in these IV. Can Feedings be Supplemented by Low animals at concentrations in the range of pH Fluids to Achieve the Critical pH 50 million/cc is encouraging and probably, Level? to some degree, applicable to the human. Concentrations of bacteria in infected In search of a low pH fluid well tolerated and readily available, Coca Cola (Coca shunt systems vary from about 10 million in Cola Co.) and ginger ale were tested in a bacteria/cc in turbid fluid to “TNTC” frankly purulent drainage. In dealing with manner similar to that described for pH
SELKER
ET
AL.:
EVALUATION
the common organisms (staph coagulase negative, E. Coli and pseudomonas), their escape from the barrier in small quantities or even in their entirety seems of little consequence to the normal function, flora or colonization of the gastro-intestinal tract. Fungi, T.B., or viral CSF involvement, however, could have an adverse effect and no precedent for the protective ability of the barrier on these entities has been established. The result of long-term infection in CSF may lead to loculation within the ventricular system under conditions of extremely low intraventricular pressure, but precedence for at least 1 yr of infected drainage with subsequent clearing on medication has been documented [8]. Further, should successful implantation in the stomach be carried out in an infant or child, regurgitation and aspiration could prove detrimental with the infection spreading to involve the lungs. However, antibiotic therapy, and an adequate cough reflex should be sufficient to minimize this effect as it does with normal gastric content in infants where vomiting is common. Our findings of over a 90% kill rate correlates well with the other published studies in the literature [5].
OF
THE
“GASTRIC
BARRIER”
545
been established for a successful kill rate after 15 min of exposure, documenting the barrier theory to be a function of pH and time of exposure. The use of low pH supplement feedings (Coca Cola and ginger ale) is feasible and may be desirable. Some possible disadvantages when employed clinically are enumerated. REFERENCES 1. Battle, H. J. and Harkins, M. J. The gastric secretion: Its bactericidal value to man. Amer. J. Med. Sci. 169:373-388, 1925. 2. Fleming, A., and Allison, V. Observations on a bacteriolytic substance (“Lysosyme”) found in secretions and tissues. Brit. .I. Exp. Path. 3:252, 1922. 3. Folks, E. and Allen, M. Occult infection of ventriculo-atria1 shunts. J. Neurosurg. 33:517, 1970. 4. Giannella, R. A., Broitman, S. A., and Zamcheck, N. Gastric acid barrier to ingested micro-organisms in man. Gut. 13:251-256, 1972. 5. Giannella, R. A., Broitman, S. A. and Zamcheck, N. Influences of gastric acidity on bacterial and parasite enteric infections. Ann. Int. Med. 78:271-276, 1973. 6. Hewetson, J. T. The bacteriology of certain parts of the human alimentary canal and the inflammatory processes arising therefrom. Br. Med. J. 2:1457-1460, 1904. 7. Knott, F. A. The gastric germicidal barrier. Guys Hosp. Rep. 73:429-437,1923.
SUMMARY The hist.orical background, rational and experimental evidence for the presence and function of a “gastric barrier” has been reviewed. In vitro and in vivo experiments were carried out to determine the effect of pH on common CSF shunt infecting organisms. A critical pH level of 3.5-3.8 has
8. Murtaugh, F. Personal Communication, 1972. 9. Reigel, D. H., Larson, 8. J. and Sances, A. Jr. The cerebral inhibition of gastric acid. Wk. Med. J. 69:163, 1970. power of intestinal 10. Soli, U. Bactericidal mucosa. Pediatria 29:97, 1921. 11. White, R., Dakters, G., Yashon, D. and Albin, M. Temporary control of cerebrospinal fluid volume by means of an externalized valve drainage system. J. Neurosurg. 30:264, 1969.
0F
SURGICAL
RESEARCH
Experimental
16,
541645
(1974)
Evaluation
of the “Gastric
Shunt ROBERT
G. SELKER,
M.D.,* AND
DAVID
SIDNEY
BAHNSON, K.
From the Departments of Surgery and Medicine, University of Pittsburgh School of Medicine and the Montefiore Hospital, Pittsburgh, Pa. *Author’s Address: Dr. Robert G. Selker, Montefiore Hospital, 3459 Fifth Avenue, Pittsburgh, Pa. 15213. Submitted for publication January 19, 1974.
WOLFSON,
M.D.,
CARL
JR.,
M.D.
A. NORDEN,
M.D.,
staphylococcus, pseudomonas, serratia, E. Coli and infrequently aerobacter. The treatment currently employed involves intraventricular and systemic antibiotics with total removal of the shunt and/or externalization of the system for decompression and drainage purposes while treatment is being effected. Even then, many return reinfected. As a matter of fact, a large percentage of asymptomatic children undergoing elective revision (Ventriculo-atria1 shunts) will show positive cultures of cerebrospinal fluid (CSF) and of the catheter tip [3]. In the course of ones practice, most every neurosurgeon has noted the fact that externalization of the shunt with drainage into an outside reservoir (so called 5th ventricle) will render the child afebrile, bright, and an eager eater [ll]. It seems apparent that children can co-exist with an infected system without continuous antibiotic therapy as long as external drainage is continued. This has been confirmed in older children permitting their return to school and normal activity. Their infection could not be cleared sufficiently to allow implantation either into the vascular system or into the peritoneal cavity [S]. Thus, the experience of others corroborates our experience where fever, positive blood cultures, lethargy, and vomiting secondary to an infected shunt system can be reversed and maintained by instituting external drainage. Should the CSF not become sterile with repeated efforts, it seems reasonable to assume that if drainage were instituted into a body organ system and there
541 @ 1974 by Academic Press, Inc. of reproduction in anyjform reserved.
in CSF
Infections
THE CONCEPT OF A “GASTRIC BARRIER” to ingested organisms can be traced as far back as the turn of the century when it was described in association with bacterial dysenteries [7, 6, I]. The exact makeup and character of the barrier was, at the time, the object of a great deal of experimental effort and speculation. Secreted mucus, mucus membrane of the small intestine, type of food and its preparation, pepsin, bile, and lysozyme were all considered and soon abandoned [lo, 1, 21. As described by Giannella et al. in their review of the subject [4], it remained for others to show that patients with reduced or absent gastric acid secretions were more susceptible to bacterial dysenteries. Their repeated work with the bacteriocidal activity of normal and achlorhydric gastric juice established again the currently accepted concept that the “gastric barrier” is, in fact, the pH level of gastric secretion. Further, that a pH of less than 4 will kill 99% of most bacteria within a 30-min period of exposure, with other constituents of gastric juice contributing little if any detectable effect [5]. One of the major disadvantages of current shunt systems is the frequency with which they become infected. The common organisms include a coagulase negative
Copyright All rights
Barrier”
542
JOURNAL
OF SUHGICAL
RESEARCH,
voL.
16, x0. 5, nfAY 1974
Table 1. Changes in Gastric pH with Feeding Time
Average
High
Low
Standard deviation
Standard error
2.32 4.78 3.62 2, -50 2.08
3.6 6.4 4.8 4 3
1.4 2. 8 2. 4 1.5 1 5
..57 1.00 .78 .86 .44
,170 31.5 ,246 .273 ,140
Fasting 15 min post feeding SO min post feeding 60 min post feeding 120 min post feeding
2.8
prolonged external rendered harmless, drainage would be avoided. Such a site would be the gastric fundus, where a protective effect to colonization by the “gastric barrier” exists. In order to assess the potential use of this ‘Lbarrier” in infected shunts, several questions became immediately evident. A. What is the normal fasting pH of the infant and/or child? What is the buffering effect of normal milk and/or formula feeding? B. What is the effect of pH on the common shunt bacteria and the necessary duration of exposure to render them nonviable? C. At what concentration of bacteria can the ‘(gastric barrier” be overcome? D. Can feedings be supplemented by low pH fluids to achieve the critical level necessary to maintain the gastric barrier? To answer these questions the following experiments were undertaken. EXPERIMENTAL DATA RESULTS
AND
I. Normal Fasting pH of Infants and Children. Buffer Effect of Milk or Formula. Ten patients ranging in ages from 2 months to 9 yr were subjected to nasogastric intubation. Attempts were made to be certain of its position within the gastric fundus. Samples of gastric juice were analyzed for pH values in the fasting state, during natural sleep and anesthesia as well as 15, 30, 60, and 120 min after feeding. The pH of Enfamil@, Prosobee@, and milk were determined and found to be 6.4, 6.9, and 6.5 respectively.
The results of gastric pH analysis revcaled the following average values in infants being fed milk, Enfamil, or Prosobee (Mead Johnson). Fasting 15 min 30 min 60 min 120 min
state post post post post
feeding feeding feeding feeding
2.3 4.78 3.62 2.50 2.08
Values during natural sleep generally agreed with the fasting values, but time of sleep came most after 30 min of feeding, making it difficult to determine it as a separate category. Determinations during anesthesia range from 2-6.5 without a reasonable cluster of values. In general, it would appear to elevate the pH values, indicating a lesser acid concentration. From this data, it would appear quite evident that the feedings, especially milk, Enfamil@ and Prosobee@ (comparable pHs) have considerable buffering effect on the pH fasting values Table 1. pH values in the one older child with a normal house diet were essentially the same for the fasting sample but varied considerably with the menu of the day, ice cream and milk intake as well as with carbonated beverages. II. Effect of pH on Common Shunt Bacteria and the Necessary Ilura tion of Exposure. To determine the effect of pH on a common shunt contaminants, an elaborate experimental system utilizing staphylococcus albus and pseudomonas aeroginosa was undertaken in the following manner. a. The hospital laboratory provided an overnight growth of staphylococcus albus
SELKER
ET
AL.:
EVALUATION
and pseudomonas in trypticase soy broth, known to be in a stationary growth phase and which, on subsequent plating and colony count, was found to contain 10” colonies/cc. b. One cc aliquot of overnight stable growth phase solution (10” bacteria/cc) was added to 9 cc of buffered trypticase soy broth with pH values of 2, 3, 4 and 5. Stock buffer solutions were prepared using Coleman Certified Buffer Tablets (Distributed by The Perkin-Elmer Corp., Rlaywood, Ill.), a preparation to which no preservative is added (most stock pH solutions contain formalin). c. Each buffered pH solution containing the added bacteria was then sampled at 0, 15, 30, 60, and 120 min of exposure to the solution by removing a 1 cc aliquot, serially diluting this aliquot in trypticase soy broth and placing these aliquots in sterile petri dishes overlayed with sterile trypticase soy agar. d. All petri dishes were incubated for 24 hr at 37°C at which time colony counts were carefully made. Results. Results are expressed as a function of time and pH. Colony counts are expressed as absolute numbers or with the notation “too numerous to count” (TNTC) (Table 2). All pH solutions at 0 min of exposure revealed unhibited growth. At I5 min of exposure it became evident that very few colonies survived in solutions of less than pH 3 and were uninhibited in growth at pH over 4. All samples allowed 30 min exposure to solutions of pH 3 or less, revealed no
OF
THE
“GASTRIC
543
BARRIER”
growth following 24 hr of incubation It seems evident that a critical lethal pH existed somewhere between a pH 3 and pH 4 for bacteria exposed 15 min or more to the solution. Additional experiments lead us to believe this to be between 3.5 and 3,.&. Although the results graphically portrayed are for staphyloccus albus and pseudomonas almost identical values were obtained with overnight inoculums of serratia and E. Coli. III. Can the “Gastric Barrier” be Overcome? If so, at What Concentration? In order to determine the effect of large concentrations of bacteria upon the gastric barrier and to test the hypothysis in vivo, a primate model was established. The fasting gastric pH of the stumptailed macaques has previously been reported and this information was utilized in consideration of a primate model [9]. Although a formal gastric analysis was not performed in our animals, random fasting samples of gastric juice revealed comparable values. Two unstandard laboratory baboons selected (papio anubis) were subjected to surgery wherein a red rubber tube was securely placed in the fundus portion of the stomach. A subcutaneous tunnel was then created through the anterior chest wall, and continued laterally and posteriorly as well as superiorly to emerge over the occiput of the animal. Having been previously trained to sit for days in a special laboratory training chair, the operated monkeys were allowed to again stabilize and obtain a basal resting state with a normal gastric
Table 2. Results of Colony Counts of Staphylococcus and Pseudomonas using an Undiluted Overnight Culture Exposure time 0 15 30 60 120
min min min min min
B TNTC-too
numerous
PHI
PH
TNT0 60 0 0 0
TNTC 81 0 0 0
to count.
3
pH 3.5 TNTC 90 0 0 0
pH4
pH5
TNTC TNTC TNTC TNTC TNTC
TNTC TNTC TNTC TNTC TNTC
544
JOURNAL
OF
SURGICAL
RESEARCH,
VOL.
16,
NO.
t$
MAY
1974
fluids of 2, 3, 4, and 5. One cc of standard (109 overnight growth phase bacteria bacteria/cc) was diluted in 9 cc of Coca Cola and exposed for 0, 15, 30, 60, and 120 min. One cc aliquots of each time period were then placed in sterile petri dishes overlayed with trypicase soy agar and incubated for 24 hr at 37°C. Colony counts were performed as with original pH ohs- 15) solutions. 120 30 60 Tlme in minutes Results. No growth occurred after 15 min Fig. 1. Effect of coca cola (pH 2.2) on a 1 cc of exposure of the bacteria to Coca Cola. aliquot of overnight culture of stnph albus or Uninhibited growth was noted at 0 min and pseudomonas. similar experiments with ginger ale (pH 2.7) revealed similar results (Fig. 1). acid content uninfluenced by anesthesia or sedation. When sufficiently acclimated to the chair and tube, serial control stool cultures were obtained by rectal swab on three consecutive days. Utilizing a laboratory strain of pigmented “red” serratia in stable congrowth phase, solutions containing centrations between 1 and 50 million bacteria/cc were infused via the implanted tube at the rate of 0.5 cc/min. for 24 hr. Twenty-four-hr periods of no infusion were permitted to elapse between each concentration increase of 10 million bacteria. Serial rectal swabs were performed on a daily basis. Results. Throughout the entire experiment, no evidence of pigmented serratia ever appeared in the stool cultures to indicate a ‘(break” in the animal ‘[gastric barrier.” Feedings throughout this time consisted of standard Rockland Primate Stars, supplemented by apples. At no time was the animal given milk or any buffering substance as would normally occur in an infant.
DISCUSSIOX
The gastric barrier as described, has, by virtue of its pH, a protective effect against ingested bacteria. From a clinical point of view its effect in bacterial dysenteries is well documented in the literature. Its utilization, with persistent CSF shunt infections seems clearly quite reasonable. The average resting pH in an infant of approximately 2.6 is well below our established critical level of 3.5-3.8. During times of feeding the buffering effect of milk or Enfamil is dramatic, even though the greatest outpouring of gastric acid would be expected at that time. The experimental finding of t’he effectiveness of the pH of Coca Cola is surprising and pleasing in view of the uniform acceptability of this beverage. Although almost equal volumes of milk and Coke (Coca Cola Co.) are required to achieve a pH of less than 4 in vitro, no account has been made for gastric acid secretion in vivo during feeding. Confronted with a specie difference and an inherently lower gastric pH in baboons, the finding of gastric barrier protection in these IV. Can Feedings be Supplemented by Low animals at concentrations in the range of pH Fluids to Achieve the Critical pH 50 million/cc is encouraging and probably, Level? to some degree, applicable to the human. Concentrations of bacteria in infected In search of a low pH fluid well tolerated and readily available, Coca Cola (Coca shunt systems vary from about 10 million in Cola Co.) and ginger ale were tested in a bacteria/cc in turbid fluid to “TNTC” frankly purulent drainage. In dealing with manner similar to that described for pH
SELKER
ET
AL.:
EVALUATION
the common organisms (staph coagulase negative, E. Coli and pseudomonas), their escape from the barrier in small quantities or even in their entirety seems of little consequence to the normal function, flora or colonization of the gastro-intestinal tract. Fungi, T.B., or viral CSF involvement, however, could have an adverse effect and no precedent for the protective ability of the barrier on these entities has been established. The result of long-term infection in CSF may lead to loculation within the ventricular system under conditions of extremely low intraventricular pressure, but precedence for at least 1 yr of infected drainage with subsequent clearing on medication has been documented [8]. Further, should successful implantation in the stomach be carried out in an infant or child, regurgitation and aspiration could prove detrimental with the infection spreading to involve the lungs. However, antibiotic therapy, and an adequate cough reflex should be sufficient to minimize this effect as it does with normal gastric content in infants where vomiting is common. Our findings of over a 90% kill rate correlates well with the other published studies in the literature [5].
OF
THE
“GASTRIC
BARRIER”
545
been established for a successful kill rate after 15 min of exposure, documenting the barrier theory to be a function of pH and time of exposure. The use of low pH supplement feedings (Coca Cola and ginger ale) is feasible and may be desirable. Some possible disadvantages when employed clinically are enumerated. REFERENCES 1. Battle, H. J. and Harkins, M. J. The gastric secretion: Its bactericidal value to man. Amer. J. Med. Sci. 169:373-388, 1925. 2. Fleming, A., and Allison, V. Observations on a bacteriolytic substance (“Lysosyme”) found in secretions and tissues. Brit. .I. Exp. Path. 3:252, 1922. 3. Folks, E. and Allen, M. Occult infection of ventriculo-atria1 shunts. J. Neurosurg. 33:517, 1970. 4. Giannella, R. A., Broitman, S. A., and Zamcheck, N. Gastric acid barrier to ingested micro-organisms in man. Gut. 13:251-256, 1972. 5. Giannella, R. A., Broitman, S. A. and Zamcheck, N. Influences of gastric acidity on bacterial and parasite enteric infections. Ann. Int. Med. 78:271-276, 1973. 6. Hewetson, J. T. The bacteriology of certain parts of the human alimentary canal and the inflammatory processes arising therefrom. Br. Med. J. 2:1457-1460, 1904. 7. Knott, F. A. The gastric germicidal barrier. Guys Hosp. Rep. 73:429-437,1923.
SUMMARY The hist.orical background, rational and experimental evidence for the presence and function of a “gastric barrier” has been reviewed. In vitro and in vivo experiments were carried out to determine the effect of pH on common CSF shunt infecting organisms. A critical pH level of 3.5-3.8 has
8. Murtaugh, F. Personal Communication, 1972. 9. Reigel, D. H., Larson, 8. J. and Sances, A. Jr. The cerebral inhibition of gastric acid. Wk. Med. J. 69:163, 1970. power of intestinal 10. Soli, U. Bactericidal mucosa. Pediatria 29:97, 1921. 11. White, R., Dakters, G., Yashon, D. and Albin, M. Temporary control of cerebrospinal fluid volume by means of an externalized valve drainage system. J. Neurosurg. 30:264, 1969.