Indian Journal of Critical Care Medicine July 2014 Vol 18 Issue 7
is true, it is not clear how the child was resuscitated at the presentation with a likely intoxication. Were gastric washing and gavage of an absorbent agent implemented? Was a toxicologist consultation requested for the patient despite the fact methemoglobinemia was not responded to intravenous methylene blue and presence of likely occurrence of a chemical exposure? By the way, how the authors have ruled out one the most important etiologies of methemoglobinemia in toxicologic settings, namely aluminum phosphide, that is the cause of great burden of morbidity and mortality in countries such as India.[2]
5. 6. 7. 8.
9.
Toxic-induced methemoglobinemia occurs in a diverse variety of drug and chemical exposures with oxidizing mechanisms.[3] Although in some reported cases, it has been shown that methemoglobinemia can develop in more rare situations such as acetaminophen overdose,[4,5] metoclopramide overdose,[6] and aluminum phosphide poisoning,[7] but the mechanism of action is more complex and less elaborated. Mostafazadeh et al. in a case series study showed that methemoglobinemia develops in aluminum phosphide poisoning in some degrees, but severe methemoglobinemia requiring therapeutic intervention is a rare finding.[8] Furthermore, Shadnia et al. have described that methemoglobinemia in aluminum phosphide poisoning is unresponsive to methylene blue administration.[7] This poisoning, in this case, could be ruled out by a bedside rapid spot test by silver nitrate impregnated paper.[9] Furthermore, anemia, in this case, has intensified the severity and lack of response to conventional treatment.
Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.136087
Role of acidic pH of intravenous fluids in subsequent development of metabolic acidosismay not be what it seems
As noted by authors, chemical exposure is one of the causes of inadequate response to methylene blue therapy in methemoglobinemia, and I think aluminum phosphide poisoning should be borne in mind in cases in which therapy seems to be resistant to methylene blue and ascorbic acid. Thank you for the interesting case discussion.
Sir, We extend our thanks to Singh et al. for drawing attention toward the controversies surrounding the use of acidic intravenous fluids (IVFs) infusion.[1] They have rightly mentioned the propensity of 5% dextrose (D5) and 0.9% saline (NS) to cause thrombophlebitis and other deleterious effects.[1] But unlike mentioned by the authors, current literature discusses the known and putative reasons for the pH of 5.5 of NS.[2] Dissolved CO2 from atmosphere, the ionic composition of the solution and inherent properties of the packaging material in which the solutions are supplied, are thought to determine it.[2] We believe that the same set of reasons may also explain the acidic pH (4.2) of D5.
Seyed Mostafa Mirakbari
Department of Forensic Medicine and Toxicology, Bu Ali Hospital, Qazvin University of Medical Sciences, Qazvin, Iran
Correspondence: Dr. Seyed Mostafa Mirakbari, Department of Forensic Medicine and Toxicology, Bu Ali Hospital, Qazvin University of Medical Sciences, Qazvin 34137-86165, Iran. E-mail: [email protected]
References 1. 2. 3. 4.
484
Pharmacol Ther 2009;32:585-95. Kanji HD, Mithani S, Boucher P, Dias VC, Yarema MC. Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity. J Popul Ther Clin Pharmacol 2013;20:e207-11. Kearns GL, Fiser DH. Metoclopramide-induced methemoglobinemia. Pediatrics 1988;82:364-6. Shadnia S, Soltaninejad K, Hassanian-Moghadam H, Sadeghi A, Rahimzadeh H, Zamani N, et al. Methemoglobinemia in aluminum phosphide poisoning. Hum Exp Toxicol 2011;30:250-3. Mostafazadeh B, Pajoumand A, Farzaneh E, Aghabiklooei A, Rasouli MR. Blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome. J Med Toxicol 2011;7:40-3. Chugh SN, Ram S, Chugh K, Malhotra KC. Spot diagnosis of aluminium phosphide ingestion: An application of a simple test. J Assoc Physicians India 1989;37:219-20.
Patnaik S, Natarajan MM, James EJ, Ebenezer K. Methylene blue unresponsive methemoglobinemia. Indian J Crit Care Med 2014;18:253-5. Murali R, Bhalla A, Singh D, Singh S. Acute pesticide poisoning: 15 years experience of a large North-West Indian hospital. Clin Toxicol (Phila) 2009;47:35-8. Rehman HU. Methemoglobinemia. West J Med 2001;175:193-6. McConkey SE, Grant DM, Cribb AE. The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats. J Vet
Free acid activity is indicated by pH but the nondissociated acid molecules in a solution may not be characterized by the pH value.[2,3] Thus solutions with high titratable acid have 78
Indian Journal of Critical Care Medicine July 2014 Vol 18 Issue 7
reservoir of hydrogen ion (H+) irrespective of pH.[3] Citing the work of Gaudry et al. the authors attribute the acidity of IVFs to their method of sterilization, Gaudry et al. in their manuscript mentioned that the titratable acidity of majority of solutions under study (e.g. D5, NS) varied between 0.063 to 9.480 meq acid/l, depending on the method used for preparation and sterilization.[1,4] Gaudry et al. also mention that though many have measured the pH of common IVFs, not much data are available regarding their titratable acidity.[4] The work of Gaudry et al. dates back to 1972 and a PubMed search by us with the term ‘titratable acidity fluid/titratable acidity solution/titratable acidity infusion' revealed only two studies relevant to this discussion. These studies date back to 1973 and 2005 and only the abstracts could be retrieved by us.[3,5] Though the in vitro pH of D5 and NS is acidic, their effect on H+ balance is probably negligible.[2,4] It may be because of their low titratable acid content.[4] But metabolic acidosis accompanies infusion of these solutions.[1,2,4,6,7] This acidosis was explained by dilution of bicarbonate content in plasma.[2,6,7] Subsequently Stewart’s physiochemical approach was used to describe the in vivo effect on acid base status by IVFs.[6,7] According to the later concept, the acid–base effect of an IVF is determined by the strong ion deference (SID) and the total weak acid concentration (ATOT) of the fluid.[6,7] pH falls with decreasing SID, increasing ATOT or CO2TOT (total CO2 content) / PCO2.[6,7] As the IVFs equilibrate with ECF, they alter SID of ECF, as SID of these IVFs defers appreciably from that of plasma.[6,7] SID of D5 and NS is 0, they decrease the SID of plasma and exert an acidifying effect.[6,7] These crystalloids are devoid of any weak acids and decrease ATOT of plasma due to its diluting effect causing alkalosis.[6,7] Whereas some colloids (e.g. albumin, gelatin) itself may contribute toward ATOT of plasma, thus, acidifying it.[6,7] Although CO2TOT/PCO2 also independently influences the pH of a biological system, its contribution in determining in vivo acid base activity of an IVF is generally regarded to be low as the concentration of dissolved CO2 is itself low (about 0.012 mmol/l).[2,6,7] But it should be kept in mind that IVFs with high CO2TOT have impact on intracellular acid base status, more during rapid administration or low perfusion states.[6,7] Contrary to the prediction by Singh et al. the pH of hypertonic saline (3%) is 5.8 and it causes more acidosis than NS because of its higher osmolarity that draws more water from other body fluid compartments.[6,7] Although the pH of Hartmann`s solution is 5, its in vivo SID is 27 meq/l,
which is close to the ideal SID of 24 meq/l.[2,6,7] And despite its pH of 5, it is known to prevent infusion-related metabolic acidosis.[2,6,7] In-depth discussion on application of the concept of quantitative physical chemistry on the in vivo effect of acid base homeostasis is available.[6,7] The effect on plasma pH by solutions with same pH may be different and differing pH can have similar acid–base effects.[2,6] Thus, the effect of an IVF on plasma/ECF SID, ATOT and CO2TOT depending on the amount infused should be considered while predicting its possible in vivo effect on acid base status, not merely its in vitro pH.[1-7]
Priyam Saikia, Dipika Choudhury, Bikash B. Bora
Department of Anaesthesiology and Critical Care, Guwahati Medical College and Hospital, Guwahati, Assam, India
Correspondence: Dr. Priyam Saikia, Department of Anaesthesiology and Critical Care, Gauhati Medical College and Hospital, Guwahati - 781 032, Assam, India. E-mail: [email protected]
References 1. 2. 3.
4. 5.
6.
7.
Singh PM, Borle A, Trikha A. Are we infusing acids into our patient’s blood? Indian J Crit Care Med 2014;18:49-50. Reddi BA. Why is saline so acidic (and does it really matter?). Int J Med Sci 2013;10:747-50. Horváth K, Regös E, Varga S. Comparative testing of titrable acidity degree and pH value of infusion solutions. Ann Immunol Hung 1973;17:265-8. Gaudry PL, Duffy C, Bookallil MJ. The pH and titratable acidity of intravenous infusion solutions. Anaesth Intensive Care 1972;1:41-4. Bruegger D, Jacob M, Scheingraber S, Conzen P, Becker BF, Finsterer U, et al. Changes in acid-base balance following bolus infusion of 20% albumin solution in humans. Intensive Care Med 2005;31:1123-7. Morgan TJ. Fluid Resuscitation. In: Kellum JA, Elbers PW, editors. Stewart’s Textbook of Acid-Base, 2nd ed. UK: Lulu Enterprises Ltd.; 2009. p. 351-64. Morgan TJ. The meaning of acid-base abnormalities in the intensive care unit: Part III -- Effects of fluid administration. Crit Care 2005;9:204-11. Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.136088
79
485
Copyright of Indian Journal of Critical Care Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
is true, it is not clear how the child was resuscitated at the presentation with a likely intoxication. Were gastric washing and gavage of an absorbent agent implemented? Was a toxicologist consultation requested for the patient despite the fact methemoglobinemia was not responded to intravenous methylene blue and presence of likely occurrence of a chemical exposure? By the way, how the authors have ruled out one the most important etiologies of methemoglobinemia in toxicologic settings, namely aluminum phosphide, that is the cause of great burden of morbidity and mortality in countries such as India.[2]
5. 6. 7. 8.
9.
Toxic-induced methemoglobinemia occurs in a diverse variety of drug and chemical exposures with oxidizing mechanisms.[3] Although in some reported cases, it has been shown that methemoglobinemia can develop in more rare situations such as acetaminophen overdose,[4,5] metoclopramide overdose,[6] and aluminum phosphide poisoning,[7] but the mechanism of action is more complex and less elaborated. Mostafazadeh et al. in a case series study showed that methemoglobinemia develops in aluminum phosphide poisoning in some degrees, but severe methemoglobinemia requiring therapeutic intervention is a rare finding.[8] Furthermore, Shadnia et al. have described that methemoglobinemia in aluminum phosphide poisoning is unresponsive to methylene blue administration.[7] This poisoning, in this case, could be ruled out by a bedside rapid spot test by silver nitrate impregnated paper.[9] Furthermore, anemia, in this case, has intensified the severity and lack of response to conventional treatment.
Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.136087
Role of acidic pH of intravenous fluids in subsequent development of metabolic acidosismay not be what it seems
As noted by authors, chemical exposure is one of the causes of inadequate response to methylene blue therapy in methemoglobinemia, and I think aluminum phosphide poisoning should be borne in mind in cases in which therapy seems to be resistant to methylene blue and ascorbic acid. Thank you for the interesting case discussion.
Sir, We extend our thanks to Singh et al. for drawing attention toward the controversies surrounding the use of acidic intravenous fluids (IVFs) infusion.[1] They have rightly mentioned the propensity of 5% dextrose (D5) and 0.9% saline (NS) to cause thrombophlebitis and other deleterious effects.[1] But unlike mentioned by the authors, current literature discusses the known and putative reasons for the pH of 5.5 of NS.[2] Dissolved CO2 from atmosphere, the ionic composition of the solution and inherent properties of the packaging material in which the solutions are supplied, are thought to determine it.[2] We believe that the same set of reasons may also explain the acidic pH (4.2) of D5.
Seyed Mostafa Mirakbari
Department of Forensic Medicine and Toxicology, Bu Ali Hospital, Qazvin University of Medical Sciences, Qazvin, Iran
Correspondence: Dr. Seyed Mostafa Mirakbari, Department of Forensic Medicine and Toxicology, Bu Ali Hospital, Qazvin University of Medical Sciences, Qazvin 34137-86165, Iran. E-mail: [email protected]
References 1. 2. 3. 4.
484
Pharmacol Ther 2009;32:585-95. Kanji HD, Mithani S, Boucher P, Dias VC, Yarema MC. Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity. J Popul Ther Clin Pharmacol 2013;20:e207-11. Kearns GL, Fiser DH. Metoclopramide-induced methemoglobinemia. Pediatrics 1988;82:364-6. Shadnia S, Soltaninejad K, Hassanian-Moghadam H, Sadeghi A, Rahimzadeh H, Zamani N, et al. Methemoglobinemia in aluminum phosphide poisoning. Hum Exp Toxicol 2011;30:250-3. Mostafazadeh B, Pajoumand A, Farzaneh E, Aghabiklooei A, Rasouli MR. Blood levels of methemoglobin in patients with aluminum phosphide poisoning and its correlation with patient’s outcome. J Med Toxicol 2011;7:40-3. Chugh SN, Ram S, Chugh K, Malhotra KC. Spot diagnosis of aluminium phosphide ingestion: An application of a simple test. J Assoc Physicians India 1989;37:219-20.
Patnaik S, Natarajan MM, James EJ, Ebenezer K. Methylene blue unresponsive methemoglobinemia. Indian J Crit Care Med 2014;18:253-5. Murali R, Bhalla A, Singh D, Singh S. Acute pesticide poisoning: 15 years experience of a large North-West Indian hospital. Clin Toxicol (Phila) 2009;47:35-8. Rehman HU. Methemoglobinemia. West J Med 2001;175:193-6. McConkey SE, Grant DM, Cribb AE. The role of para-aminophenol in acetaminophen-induced methemoglobinemia in dogs and cats. J Vet
Free acid activity is indicated by pH but the nondissociated acid molecules in a solution may not be characterized by the pH value.[2,3] Thus solutions with high titratable acid have 78
Indian Journal of Critical Care Medicine July 2014 Vol 18 Issue 7
reservoir of hydrogen ion (H+) irrespective of pH.[3] Citing the work of Gaudry et al. the authors attribute the acidity of IVFs to their method of sterilization, Gaudry et al. in their manuscript mentioned that the titratable acidity of majority of solutions under study (e.g. D5, NS) varied between 0.063 to 9.480 meq acid/l, depending on the method used for preparation and sterilization.[1,4] Gaudry et al. also mention that though many have measured the pH of common IVFs, not much data are available regarding their titratable acidity.[4] The work of Gaudry et al. dates back to 1972 and a PubMed search by us with the term ‘titratable acidity fluid/titratable acidity solution/titratable acidity infusion' revealed only two studies relevant to this discussion. These studies date back to 1973 and 2005 and only the abstracts could be retrieved by us.[3,5] Though the in vitro pH of D5 and NS is acidic, their effect on H+ balance is probably negligible.[2,4] It may be because of their low titratable acid content.[4] But metabolic acidosis accompanies infusion of these solutions.[1,2,4,6,7] This acidosis was explained by dilution of bicarbonate content in plasma.[2,6,7] Subsequently Stewart’s physiochemical approach was used to describe the in vivo effect on acid base status by IVFs.[6,7] According to the later concept, the acid–base effect of an IVF is determined by the strong ion deference (SID) and the total weak acid concentration (ATOT) of the fluid.[6,7] pH falls with decreasing SID, increasing ATOT or CO2TOT (total CO2 content) / PCO2.[6,7] As the IVFs equilibrate with ECF, they alter SID of ECF, as SID of these IVFs defers appreciably from that of plasma.[6,7] SID of D5 and NS is 0, they decrease the SID of plasma and exert an acidifying effect.[6,7] These crystalloids are devoid of any weak acids and decrease ATOT of plasma due to its diluting effect causing alkalosis.[6,7] Whereas some colloids (e.g. albumin, gelatin) itself may contribute toward ATOT of plasma, thus, acidifying it.[6,7] Although CO2TOT/PCO2 also independently influences the pH of a biological system, its contribution in determining in vivo acid base activity of an IVF is generally regarded to be low as the concentration of dissolved CO2 is itself low (about 0.012 mmol/l).[2,6,7] But it should be kept in mind that IVFs with high CO2TOT have impact on intracellular acid base status, more during rapid administration or low perfusion states.[6,7] Contrary to the prediction by Singh et al. the pH of hypertonic saline (3%) is 5.8 and it causes more acidosis than NS because of its higher osmolarity that draws more water from other body fluid compartments.[6,7] Although the pH of Hartmann`s solution is 5, its in vivo SID is 27 meq/l,
which is close to the ideal SID of 24 meq/l.[2,6,7] And despite its pH of 5, it is known to prevent infusion-related metabolic acidosis.[2,6,7] In-depth discussion on application of the concept of quantitative physical chemistry on the in vivo effect of acid base homeostasis is available.[6,7] The effect on plasma pH by solutions with same pH may be different and differing pH can have similar acid–base effects.[2,6] Thus, the effect of an IVF on plasma/ECF SID, ATOT and CO2TOT depending on the amount infused should be considered while predicting its possible in vivo effect on acid base status, not merely its in vitro pH.[1-7]
Priyam Saikia, Dipika Choudhury, Bikash B. Bora
Department of Anaesthesiology and Critical Care, Guwahati Medical College and Hospital, Guwahati, Assam, India
Correspondence: Dr. Priyam Saikia, Department of Anaesthesiology and Critical Care, Gauhati Medical College and Hospital, Guwahati - 781 032, Assam, India. E-mail: [email protected]
References 1. 2. 3.
4. 5.
6.
7.
Singh PM, Borle A, Trikha A. Are we infusing acids into our patient’s blood? Indian J Crit Care Med 2014;18:49-50. Reddi BA. Why is saline so acidic (and does it really matter?). Int J Med Sci 2013;10:747-50. Horváth K, Regös E, Varga S. Comparative testing of titrable acidity degree and pH value of infusion solutions. Ann Immunol Hung 1973;17:265-8. Gaudry PL, Duffy C, Bookallil MJ. The pH and titratable acidity of intravenous infusion solutions. Anaesth Intensive Care 1972;1:41-4. Bruegger D, Jacob M, Scheingraber S, Conzen P, Becker BF, Finsterer U, et al. Changes in acid-base balance following bolus infusion of 20% albumin solution in humans. Intensive Care Med 2005;31:1123-7. Morgan TJ. Fluid Resuscitation. In: Kellum JA, Elbers PW, editors. Stewart’s Textbook of Acid-Base, 2nd ed. UK: Lulu Enterprises Ltd.; 2009. p. 351-64. Morgan TJ. The meaning of acid-base abnormalities in the intensive care unit: Part III -- Effects of fluid administration. Crit Care 2005;9:204-11. Access this article online Quick Response Code: Website: www.ijccm.org
DOI: 10.4103/0972-5229.136088
79
485
Copyright of Indian Journal of Critical Care Medicine is the property of Medknow Publications & Media Pvt. Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
