Abstract
Introduction:
Hydrogen ion concentration which is expressed as pH value is in human blood maintained in narrow physiological range (7.36-7.44 in arterial blood). This range is crucial for normal functioning of most biochemical reactions. Extreme acidosis with pH < 6.8 is incompatible with life, unless pathophysiologic process is rapidly reversed. Timely, standardized, and structured approach to assessment and management of extreme critical illness is essential to maximize the chances of patient’s survival.
Cases:
We present a series of 3 critically ill patients admitted to Medical intensive care unit (MICU) diagnosed with extreme metabolic acidosis (pH ⩽ 6.8). Each patient was treated using
Discussion:
Medical physiology textbooks set the lower limit of pH value at which life is possible to 6.8. However, examples from clinical practice show that if adequate resuscitation measures are taken early in the acute phase of the disease, the biochemical cascade of reactions that are considered irreversible (at pH ⩽ 6.8) may be reversed after all.
Conclusion:
Critical care approach to extreme metabolic acidosis is a prime example of applied clinical physiology where basic science and clinical practice connect. With these case series we show that timely and structured approach to critical illness shifts the boundaries of reversibility for some of the most severe physiologic derangements.
Introduction
Acid-base balance or hydrogen ion homeostasis (expressed as pH value) is crucial for normal functioning and metabolism of all cells, tissues, and organs. In human organism, acid-base balance is maintained keeping the pH value of arterial blood in narrow range of 7.36 to 7.44. Each oscillation of pH value outside of this range represents potential hazard for many essential metabolic and enzyme systems as well as transmembrane transport processes which in clinical sense can lead to cardiorespiratory failure.1,2
Physiological buffer systems along with lungs and kidneys try to prevent pH value oscillations outside the defined range and in that way enable normal functioning of all cells, tissues, and organs in human body. 3 However, these compensatory mechanisms are not always effective and sufficient, especially in acute illness and if resuscitation measures are not available.
One of these conditions include extreme acidosis for which we know that leads to functional disorders at molecular level and which clinically manifests in change of functioning of most organs and organ systems. There are various causes of severe metabolic acidosis but it is mostly seen in clinical disorders such as ketoacidosis, sepsis, and hypovolemia. 4
Acutely, acidosis jeopardizes oxygenation, has depressive effect to heart contractility, causes arrhythmia and increase in pulmonary vascular resistance. Additionally it increases the chance of coagulopathy, leads to disturbance in thermoregulation. Vital proteins’ configuration is altered in acidosis leading to its dysfunction. Severe acidosis can cause extremely resistant peripheral vasodilatation which requires administration of high doses of vasopressors. Possible cause of this might be decreased affinity of inotrope and vasopressor receptors.5-7
Patients with severe acid-base disorders require treatment in intensive care units with prompt reaction from critical care physicians. It is essential to provide a rapid, structured assessment, and early adequate resuscitation to stop and reverse potentially fatal pathophysiological derangements in order to lower the mortality rate of patients presenting with extreme acidosis.
Case Series Report
We present 3 critically ill patients with severe metabolic acidosis characterized by different etiologies. Patients were initially admitted and treated in medical intensive care unit (MICU) of University Clinical Centre Republic of Srpska, where CERTAIN platform (
Table 1 presents a structured overview of all 3 cases. Interpretation of clinical data along with laboratory, radiological and results of other diagnostic procedures is of great help in the rapid establishment of a working diagnosis and the most acceptable therapeutic modalities.
Case series presentation using structured approach.
Clinical Observations, Initial Diagnostic and Treatment Approach: Resuscitation Measures and Outcome
Patient 1
Through clinical assessment of the patient we noted pale skin, hypotension, hypothermia and anuria. We learned about patient’s hematemesis through heteroanamnesis. Test results revealed severe anemic syndrome (Hb 31 g/L) without coagulation cascade disorder. pH value was 6.78 and lactate level was 20.4 mmol/L. It was concluded that patient is in hypovolemic (hemorrhagic) shock and previously started resuscitation with oxygen (IV fluids, blood derivatives, vasopressors, haemostatic, and other symptomatic-supportive measures) was continued for 24 hours after which patient’s vital functions were stabilized. Gastrointestinal endoscopy revealed huge amount of blood in patient’s stomach without bleeding source visualization at that moment. On the third day of MICU hospitalization, it was decided to transfer the patient to gastroenterology ward where in further examination infiltrative change in stomach was found. Tissue sample of patient’s stomach was taken for further histopathology analysis.
Patient 2
Through clinical assessment of the patient, we noted hypotension and anuria, along with changes in ECG in sense of bradycardia with high T waves. Patient has been suffering from rheumatoid arthritis and diabetes mellitus and has used insulin and methotrexate with folic acid regularly. Laboratory analysis revealed increased markers of inflammation, hyperkalemia (7.7 mmol/L), increased lactate levels (10.4 mmol/L), extremely increased urea and creatinine levels (45.5 mmol/L and 1245 μmol/L, respectively), with acidemia and pH value of 6.79. The urinary sediment analysis showed pathological findings. It was concluded that severe acidosis was caused by acute renal failure which was triggered by urosepsis. Resuscitation with oxygen, IV fluids, vasopressors, corticosteroids, wide spectrum antibiotics, and other symptomatic-supportive measures was started immediately. CVVHD was started and was continued for 24 hours along with all other resuscitation measures after which patient’s heart rate finally stabilized. Vasopressor doses were initially decreased and then stopped. Patient’s diuresis was regained. After 7 days of hospitalization in the MICU, patient’s vital functions became stable. There was no need for further dialysis and we decided to transfer the patient to step down unit—hematology ward, due to evident decrease in values of all types of blood cells for further diagnostic evaluation. Blood smear analysis led to conclusion that methotrexate was the probable cause of hematologic disorder. After provision of adequate therapeutic measures, patient fully recovered, and was discharged from the hospital.
Patient 3
On admission patient’s level of conciseness was determined (GCS 7) and painful abdomen was detected. Abdominal surgeon was consulted and urgent ultrasound and CT of patient’s abdomen were performed, which both came back normal. Hence, acute intrabdominal and other surgical disorders were excluded. Through heteroanamnesis, it was found out that patent has had diabetes mellitus for many years. Laboratory analysis of patient’s blood revealed leukocytosis, pH value of 6.65, bicarbonate level of 1.8 mmol/L and lactate level of 4.2 mmol/L. Extremely high values of glucose were detected, despite the fact that short acting insulin was self-administered by patient at home shortly before arrival to hospital. Due to disturbed conciseness and inadequately functioning airway, patient was intubated and controlled mechanical ventilation was started. Diabetic ketoacidosis was suspected, triggered most probably by infection with unknown locus. Resuscitation was started immediately with IV fluids, vasopressor, empirical wide-spectrum antimicrobial therapy, continuous IV infusion of insulin, IV electrolytes, and other symptomatic and supportive measures which eventually led to regulation of acid-base status and clinical recovery of the patient. On the fourth day of MICU hospitalization, it was decided to transfer the patient to step down unit -endocrinology ward. In the next few days, adequate glycemic control was achieved, and patient was discharged from the hospital.
Discussion
Medical physiology textbooks set the lower limit of pH value at which life is possible to 6.8. However, examples from clinical practice show that if adequate resuscitation measures are provided early in the acute phase of the disease, the biochemical cascade of reactions that were considered irreversible at some point (at pH ⩽ 6.8) may be reversed after all.10,11 Case series presented here, confirm these statements.
In the first case report, patient experienced hypovolemic (hemorrhagic) shock. It is well known that untreated hypovolemic shock leads to severe acidosis, and that only 1 out of 3 patients survives initial resuscitation.10,12 Mortality rate in acidosis caused by hemorrhagic shock is 86% as shown in clinical studies with small size samples. 11 It is considered that providing fast resuscitation measures to patient with severe hemorrhagic shock and metabolic acidosis can lead to patient’s survival. It is proven that presence of multiorgan disfunction impacts survival rate. Case report found in the literature shows successful treatment of polytraumatized patient in hemorrhagic shock with metabolic acidosis and pH value of 6.5. 13 In situations like this, acidosis is always triggered by tissue hypoperfusion, and without oxygen supplementation, conditions for anabolic metabolism and excessive lactate production are met. Identical pathophysiological mechanism is seen in patient case we described. Lactate level is always in correlation to hypoperfusion severity; on the other side lactate level is biomarker of hemorrhagic shock. Fast volume and blood cells repletion along with oxygen therapy was crucial in resuscitation of patient presented in this case report. In addition, correction of severe acidosis (and hypothermia) is important for adequate coagulation and hemostasis. 14
Second case report describes patient with acute renal failure most likely triggered by sepsis. Kidneys are frequently affected by impaired oxygen balance due to impaired perfusion in all forms of shock. Hypoperfusion may also lead to increase in serum creatinine and blood urea nitrogen levels, which are the most commonly used biomarkers of renal function.
These findings along with detected metabolic acidosis were dominant in second patient case. Sepsis induced peripheral vasodilatation, fall in arterial pressure, and renal hypoperfusion in patient causing acute renal failure and expression of its signs: hyperkalemia, increase in level of hyperosmolar compounds and acid-base disorder. Patient’s organism was pulled into vicious circle where treatment usually becomes ineffective due to severe acidosis. Both lactic acidosis and acute renal failure contributed to development of extreme metabolic acidosis in this patient. 15 Renal replacement therapy is necessary when uremic symptoms develop with excess extracellular volume, hyperkalemia, or metabolic acidosis refractory to medical therapy. Continuous renal replacement therapies can be used for fluid removal (ultrafiltration) or solute removal (dyalisis, hemofiltration, hemodiafiltration). An appropriate selection depends on the circumstances around the individual patient (especially his or her hemodynamic status). 16 Only after starting continuous veno-venous hemodiafiltration (CVVHDF) the patient’s condition started to improve.
Third case report describes a patient with classical diabetic ketoacidosis which represents acute metabolic complication of diabetes mellitus characterized by hyperglycemia, hyperketonemia, and metabolic acidosis. Hyperglycemia leads to osmotic diuresis and is much more often seen in diabetes mellitus type I. It is manifested with nausea, vomiting, and abdominal pain which was dominant symptom in presented patient, and if fast resuscitations measures are not applied, patient’s condition can complicate to brain edema, coma and death. 17 Diagnosis is made due to presence of hyperketonemia, metabolic acidosis with anion gap and hyperglycemia. Treatment includes volume resuscitation, insulin administration and hypokalemia prevention. Insulin normally inhibits ketogenesis, hence in lack of insulin ketone products are created which can lead to metabolic acidosis. 18 Elevated lactate levels are often seen in diabetic ketoacidosis, and those are consequence of inadequate tissue perfusion (due to decrease in intravascular volume, presence of micro- and macroangiopathy, increase in glycolyzed hemoglobin, and abnormal platelet function). Further, hypoxemia stimulates process of anaerobic glycolysis where pyruvate is metabolized to lactate along with 2 molecules of adenosine triphosphate (ATP).19,20 In general, diabetic acidosis is associated with higher survival rates compared to other causes of extreme metabolic acidosis (pH < 6.8).
Conclusion
Blood gas analysis along with acid-base status interpretation represent example of connection between basic physiology science and clinical practice.
These clinical practice examples can serve to show that development of modern intensive care medicine with adequately trained critical care staff, adequate space, and equipment, and the structured approach to critical illness during golden hours shifts the boundaries of reversibility of even extreme acute physiological impairments.
Regardless of the etiology of severe metabolic acidosis, it has been shown that timely initiation of adequate resuscitation procedures along with other specific and symptomatic measures is a key link in the successful treatment of these patients.
Footnotes
Appendix
Funding:
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests:
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Author Contributions
Sasa Dragic, Danica Momcicevic, Biljana Zlojutro, Milka Jandric and Tijana Kovacevic participated in the treatment of all patients and wrote this article. Vlado Djajic, Ognjen Gajic and Pedja Kovacevic read and approved the final manuscript.
Patient Consent Confirmation Statement
Appropriate consent to publish case details was obtained from the patients.