Chasing the base deficit: hyperchloraemic acidosis following 0.9% saline fluid resuscitation

Base deficit is a parameter often used to guide further treatment in acidotic children and is taken as a measure of how "sick" they are. Five children with septic shock are presented who had persisting base deficit after large volume resuscitation with 0.9% saline. Stewart''s strong ion theory of acid-base balance is able to quantify the causes of metabolic acidosis and is used to show that our patients had a hyperchloraemic metabolic acidosis. We show how the chloride content of the saline loads given to our patients caused this hyperchloraemia. It is concluded that 0.9% saline and other chloride rich fluids may not be ideal resuscitation fluids; if used, clinicians must be aware of their potential to cause a persistent base deficit.     

Fluid resuscitation therapy for paediatric sepsis

Sepsis and septic shock are the final common pathway for many decompensated paediatric infections. Fluid resuscitation therapy has been the cornerstone of haemodynamic resuscitation in these children. Good evidence for equivalence between 0.9% saline and 4% albumin, with the relative expense of the latter, has meant that 0.9% saline is currently the most commonly used resuscitation fluid world‐wide. Evidence for harm from the chloride load in 0.9% saline has generated interest in balanced solutions as first line resuscitation fluids. Their safety has been well established in observational studies, and they may well be the most reasonable default fluid for resuscitation. Semi‐synthetic colloids have been associated with renal dysfunction and death and should be avoided. There is evidence for harm from excessive administration of any resuscitation fluid. Resuscitation fluid volumes should be treated in the same way as the dose of any other intravenously administered medication, and the potential benefits versus harms for the individual patient weighed prior to administration.     

Late metabolic acidosis: a reassessment of the definition.

The term "late metabolic acidosis" is generally used to define a population of apparently healthy LBW infants who fail to grow and have a base deficit in excess of 5 mEq/l (CO2TOT less than 21 mM). A relationship between hypobasemia and the lack of appropriate growth was postulated. This conclusion was reached, however, in the absence of adequate information regarding the distribution of acid-base variables in healthy LBW infants. The results of this study demonstrate that the CO2TOT of LBW infants (n = 114) rises between birth and three weeks of life from a mean of 18.6 to 20.3 mM. The frequency distribution of CO2TOT values did not show any significant deviations from normality, and 2 SD included values as low as 14.5 mM. No difference in the rate of growth was detected between "hypobasemic" infants given a solution of bicarbonate calculated to bring their blood CO2TOT to greater than 21 mM and those given similar amounts of isotonic saline solution. The ability of the LBW infants to excrete an ammonium chloride load was not related to their acid-base status and was comparable to that of term infants. It is apparent that the definition of late metabolic acidosis needs to be reconsidered.     

Acetazolamide poisoning in a toddler

Acetazolamide ingestion and its sequelae have not been previously reported in children. A 12-month-old girl, weighing 10 kg, developed metabolic acidosis following ingestion of between 500 and 1250 mg of acetazolamide. The maximum base deficit recorded was 11.6. She was treated with sodium bicarbonate and recovered completely. Accidental poisoning should be included in the differential diagnosis of a child presenting with metabolic acidosis.     

Metabolic studies of transient tyrosinemia in premature infants.

The recently developed technique of gas chromatography-mass spectrometry supported by computer has considerably improved the analysis of physiologic fluids. This study attempted to demonstrate the value of this system in the investigation of metabolite patterns in urine in two metabolic problems of prematurity, transient tyrosinemia and late metabolic acidosis. Serial 24-hr urine specimens were analyzed in 9 infants. Transient tyrosinemia, characterized by 5-10-fold increases over basal excretion of tyrosine, p-hydroxyphenyllactate, and p-hydroxyphenylpyruvate in urine, was noted in five of the infants. Several infants had fluctuating levels of tyrosine metabolites in urine although dietary protein intake remained constant at 3-4 g/kg/24 hr and ascorbic acid at 50 mg/24 hr. Late metabolic acidosis was seen in four infants, but bore no relation to transient tyrosinemia. The ratio of net acid to urea excretion in urine increased with increasing base deficit, implying a nonprotein origin of the metabolic acid. No unique metabolic patterns were characteristic of late metabolic acidosis.     

Intravenous glycerol therapy should not be used in patients with unrecognized fructose-1,6-bisphosphatase deficiency

BACKGROUND: In Asian countries, glycerol solution that contains fructose (5%) is often used for management of brain edema. However, glycerol and fructose may cause severe hypoglycemia and metabolic acidosis in patients with fructose-1,6-bisphosphatase (FBPase) deficiency, even under stable conditions. The aim of the present study was to determine whether glycerol solution was used for brain edema during acute metabolic decompensation of hypoglycemia and metabolic acidosis in patients with unrecognized FBPase deficiency in Japan and to examine a long-term prognosis of the patients who had this kind of severe metabolic decompensation with or without glycerol therapy. METHODS: A retrospective study of 20 children with FBPase deficiency was conducted, based on their medical records. RESULTS: Six of the 20 children were given glycerol solution for the presence or possibility of brain edema during acute metabolic decompensation of hypoglycemia and metabolic acidosis; two of the six patients administered with glycerol were given dialysis. In four patients treated with glycerol alone without dialysis, two had no brain edema before glycerol administration but it developed later after the administration. These four patients treated with glycerol alone died or developed severe neurological complications. Fourteen patients who were not treated with glycerol solution had no brain edema and showed good prognosis. CONCLUSIONS: Glycerol solution, which contains fructose in Asian countries including Japan, should not be used as an osmotic agent for treatment of brain edema in patients who have hypoglycemia and retention-type metabolic acidosis, until FBPase deficiency is ruled out by measuring blood concentration of lactate.     

Hyperchloraemic metabolic acidosis following open cardiac surgery

Aims: To describe acid–base derangements in children following open cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl–Stewart strong ion approach. Methods: Prospective observational study set in the paediatric intensive care unit (PICU) of a university children''s hospital. Arterial blood gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG), and partitioned base excess (BE) were measured and calculated on admission to PICU. Results: A total of 97 children, median age 57 months (range 0.03–166), median weight 14 kg (range 2.1–50), were studied. Median CPB time was 80 minutes (range 17–232). Predicted mortality was 2% and there was a single non-survivor. These children showed mild metabolic acidosis (median standard bicarbonate 20.1 mmol/l, BE –5.1 mEq/l) characterised by hyperchloraemia (median corrected Cl 113 mmol/l), and hypoalbuminaemia (median albumin 30 g/l), but no significant excess unmeasured anions or cations (median SIG 0.7 mEq/l). The major determinants of the net BE were the chloride and albumin components (chloride effect –4.8 mEq/l, albumin effect +3.4 mEq/l). Metabolic acidosis occurred in 72 children (74%) but was not associated with increased morbidity. Hyperchloraemia was a causative factor in 53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children required adrenaline for inotropic support, compared to eight children (28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer duration of inotropic support and PICU stay. Conclusions: In these children with low mortality following open cardiac surgery, hypoalbuminaemia and hyperchloraemia were the predominant acid–base abnormalities. Hyperchloraemia was associated with reduced requirement for adrenaline therapy. It is suggested that hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an alkalinising force, was associated with prolonged requirement for intensive care.     

Hyperchloraemic metabolic acidosis following open cardiac surgery.

AIMS: To describe acid-base derangements in children following open cardiac surgery on cardiopulmonary bypass (CPB), using the Fencl-Stewart strong ion approach. METHODS: Prospective observational study set in the paediatric intensive care unit (PICU) of a university children's hospital. Arterial blood gas parameters, serum electrolytes, strong ion difference, strong ion gap (SIG), and partitioned base excess (BE) were measured and calculated on admission to PICU. RESULTS: A total of 97 children, median age 57 months (range 0.03-166), median weight 14 kg (range 2.1-50), were studied. Median CPB time was 80 minutes (range 17-232). Predicted mortality was 2% and there was a single non-survivor. These children showed mild metabolic acidosis (median standard bicarbonate 20.1 mmol/l, BE -5.1 mEq/l) characterised by hyperchloraemia (median corrected Cl 113 mmol/l), and hypoalbuminaemia (median albumin 30 g/l), but no significant excess unmeasured anions or cations (median SIG 0.7 mEq/l). The major determinants of the net BE were the chloride and albumin components (chloride effect -4.8 mEq/l, albumin effect +3.4 mEq/l). Metabolic acidosis occurred in 72 children (74%) but was not associated with increased morbidity. Hyperchloraemia was a causative factor in 53 children (74%) with metabolic acidosis. Three (4%) hyperchloraemic children required adrenaline for inotropic support, compared to eight children (28%) without hyperchloraemia. Hypoalbuminaemia was associated with longer duration of inotropic support and PICU stay. CONCLUSIONS: In these children with low mortality following open cardiac surgery, hypoalbuminaemia and hyperchloraemia were the predominant acid-base abnormalities. Hyperchloraemia was associated with reduced requirement for adrenaline therapy. It is suggested that hyperchloraemic metabolic acidosis is a benign phenomenon that should not prompt escalation of haemodynamic support. By contrast, hypoalbuminaemia, an alkalinising force, was associated with prolonged requirement for intensive care.     

Metabolic acidosis as an underlying mechanism of respiratory distress in children with severe acute asthma.

OBJECTIVE: 1) To alert the clinician that increasing rate and depth of breathing during treatment of acute asthma may be a manifestation of metabolic acidosis with hyperventilation rather than worsening airway obstruction; and 2) to describe the frequency of metabolic acidosis with hyperventilation in children with severe acute asthma admitted to our pediatric intensive care unit. DESIGN: Retrospective medical record review. SETTING: University-affiliated children's hospital. PATIENTS: All patients admitted to the pediatric intensive care unit with a diagnosis of asthma between January 1, 2005, and December 31, 2005. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Fifty-three patients with asthma (median age 7.8 yrs, range 0.7-17.9 yrs; 35 [66%] male; 46 [87%] black and 7 [13%] white) were admitted to the pediatric intensive care unit during the study period. Fifteen (28%) patients developed metabolic acidosis with hyperventilation (pH <7.35, Pco2 <35 torr [4.6 kPa], and base excess < or = -7 mmol/L) during their hospital course. Of these, lactic acid was assessed in four patients and was elevated in each; all had hyperglycemia (blood glucose >120 mg/dL [6.7 mmol/L]). Patients who developed metabolic acidosis with hyperventilation received asthma therapy similar to that received by patients who did not develop the disorder. Metabolic acidosis resolved contemporaneously with tapering of beta2-adrenergic agonists and administration of supportive care. All patients survived. CONCLUSIONS: Metabolic acidosis with hyperventilation manifesting as respiratory distress can occur in children with severe acute asthma. A pathophysiologic rationale exists for the contribution of beta2-adrenergic agents to the development of this acid-base disorder. Failure to recognize metabolic acidosis as the underlying mechanism of respiratory distress may lead to inappropriate intensification of bronchodilator therapy. Supportive care and tapering of beta2-adrenergic agents are recommended to resolve this condition.     

Early predictors of adverse outcome in term infants with post-asphyxial hypoxic ischaemic encephalopathy

A retrospective study of 35 term infants with post-asphyxial hypoxic-ischaemic encephalopathy (HIE) was conducted to identify early clinical predictors of either death or major motor disability at 18 mo of age. Twenty-three had severe adverse outcome:13 died and 10 had major neurological sequelae. The significant risk factors were a low 5 min Apgar score, use of adrenaline, low first arterial pH and high base deficit. A base deficit > or =20 mEq/L is a useful predictor of death or disability with a high positive predictive value (PPV) of 93.8%, followed by 93.3% and 84.2% for pH <7.1 and 5 min Apgar score <4, respectively. The PPV of death or disability is enhanced in the model combining base deficit of > or =20 mEq/L and 5 min Apgar score of <4. This model has a sensitivity of 66.7% and specificity of 100%. Severe metabolic acidosis of base deficit > or =25 mEq/L was associated with a high risk of dying: PPV 77.8% and specificity 88.9%.     

Defining acidosis in postoperative cardiac patients using Stewart's method of strong ion difference.

OBJECTIVE: To define the true incidence and nature of acidosis in pediatric patients postcardiac surgery, using Stewart's direct method of measuring strong ion difference. We also wished to compare the ability of standard indirect methods (base deficit, lactate, anion gap, and corrected anion gap) to accurately predict tissue acidosis. DESIGN: A single-center prospective observational study. SETTING: A pediatric intensive care unit in a tertiary referral center. PATIENTS: Pediatric patients who had undergone cardiac surgery were studied in the immediate postoperative period. Patients who had undergone both open and closed cardiac surgery were included. INTERVENTIONS: Routine arterial blood gas analysis and laboratory electrolyte measurements were made in patients immediately on admission to the pediatric intensive care unit (PICU) after cardiac surgery and each morning until discharge from the PICU. MEASUREMENTS AND MAIN RESULTS: Figge's equations were used to calculate strong ion difference and total tissue acids (unmeasured acids and lactate). These direct methods then were compared to indirect measurements: base deficit, lactate anion gap, and anion gap corrected for albumin. We collected 150 samples from 44 patients. Tissue acidosis occurred overall in 60 of 150 samples. This was due to raised unmeasured acids alone in 44 of 60 (73.3%), raised lactate alone in six of 60 (10%), and a combination of the two in ten of 60 (16.6%). Hyperchloremia occurred in 19 of 150 samples overall and 12 of 25 (48%) samples immediately after cardiopulmonary bypass. Measured base deficit showed a poor correlation with true tissue acidosis (r = -.48, p <.001) and the worst discriminatory ability (area under the curve, 0.72; 0.62-0.82). Anion gap corrected for albumin had the best correlation (r =.95, p <.001) and highest area under the curve (0.90; 0.85-0.95). CONCLUSIONS: Metabolic acidosis occurs frequently postcardiac surgery and is largely due to raised unmeasured acids and less commonly raised lactate. Hyperchloremia is common, particularly after cardiopulmonary bypass. Base deficit correlates poorly with true tissue acidosis, and corrected anion gap offers the most accurate bedside alternative to Stewart's method of tissue acid calculation.     

Oxygen delivery, oxygen consumption, and metabolic acidosis during group B streptococcal sepsis in piglets

The development of metabolic acidosis during neonatal sepsis with group B streptococci (GBS) has been attributed to progressive tissue ischemia resulting from reduced oxygen delivery (QO2). Using an animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic QO2, one septic and one not. Eighteen anaesthetized piglets were instrumented to observe aortic pressure, cardiac output, arterial and mixed venous blood gases, oxygen content, and hemoglobin concentration. QO2, oxygen consumption, and oxygen extraction ratio were calculated. Six piglets (group 1) received continuous infusion of live GBS organisms; six piglets (group 2) received continuous infusion of phenylephrine (PE), beginning with 10-micrograms/kg/min and increasing as required to match the PE-induced reduction in QO2 to the fall observed in the group 1 (GBS) piglets at each 30-min interval. Group 3 piglets (n = 6) received 0.9% saline and served as controls. No differences in either cardiac output or QO2 were noted comparing GBS and PE piglets at any time interval from 0-180 minutes. At 120, 150, and 180 minutes, both QO2 and cardiac output were lower in GBS and PE piglets compared to controls. Despite equivalent reductions in cardiac output and QO2, only GBS piglets developed significant metabolic acidosis, while pH and base deficit for PE piglets did not differ from controls. Oxygen consumption did not differ significantly among the three experimental groups at any observation time. Oxygen extraction ratio did not differ comparing PE and GBS piglets at any observation time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isotonic is better than hypotonic saline for intravenous rehydration of children with gastroenteritis: a prospective randomised study.

AIMS: To determine whether the risk of hyponatraemia in children with gastroenteritis receiving intravenous (IV) fluids is decreased by the use of 0.9% saline. METHODS: A prospective randomised study was carried out in a tertiary paediatric hospital. A total of 102 children with gastroenteritis were randomised to receive either 0.9% saline + 2.5% dextrose (NS) or 0.45% saline + 2.5% dextrose (N/2) at a rate determined by their treating physician according to hospital guidelines and clinical judgement. Plasma electrolytes, osmolality, and plasma glucose were measured before (T(0)) and 4 hours after (T(4)) starting IV fluids, and subsequently if clinically indicated. Electrolytes and osmolality were measured in urine samples. Results were analysed according to whether children were hyponatraemic (plasma sodium <135 mmol/l) or normonatraemic at T(0). RESULTS: At T(0), mean (SD) plasma sodium was 135 (3.3) mmol/l (range 124-142), with 37/102 (36%) hyponatraemic. At T(4), mean plasma sodium in children receiving N/2 remained unchanged in those initially hyponatraemic (n = 16), but fell 2.3 (2.2) mmol/l in the normonatraemic group. In contrast, among children receiving NS, mean plasma sodium was 2.4 (2.0) mmol/l higher in those hyponatraemic at baseline (n = 21) and unchanged in the initially normonatraemic children. In 16 children who were still receiving IV fluids at 24 hours, 3/8 receiving N/2 were hyponatraemic compared with 0/8 receiving NS. No child became hypernatraemic. CONCLUSIONS: In gastroenteritis treated with intravenous fluids, normal saline is preferable to hypotonic saline because it protects against hyponatraemia without causing hypernatraemia.     

Hyponatremia in hospitalized critically Ill children : Current concepts

Hyponatremia (serum sodium to <136 mEqJl) is the most common electrolyte abnormality in critically ill children. It could result from a deficit of sodium, or surplus of water. Impaired water excretion, ‘inappropriate’ release of vasopressin, use of hypotonic fluids, redistribution of sodium and water, sick cell syndrome, several drugs and primary illness all may contribute to hyponatremia. Acute hyponatremia, defined as a fall in serum sodium to -120 mEqJl within 48 hours may result in acute cerebral edema and brain stem herniation particularly in children. However, there is paucity of data on hyponatremia in hospitalized critically ill patients. Studies addressing incidence, cause and outcome of hyponatremia in critically ill patients are needed to plan rational fluid therapy protocols, and resolve the current debate, which calls for abandonment of NJ5 saline in 5% dextrose solution as maintenance intravenous fluid in favour of normal saline to prevent hyponatremia. At present it is not fully correct to assume that isotonic maintenance fluids would be superior to current maintenance fluids. Reducing the volume of maintenance fluid to about 75% of normal maintenance volume may be more appropriate way to prevent hyponatremia in view of water retaining effect of high ADH and reduced renal free water clearance in critically ill children.     

Serum anion gap in the differential diagnosis of metabolic acidosis in critically ill newborns

OBJECTIVES: To determine in critically ill newborn infants (1) the range of the serum anion gap without metabolic acidosis and (2) whether the serum anion gap can be used to distinguish newborns with lactic acidosis from those with hyperchloremic metabolic acidosis. STUDY DESIGN: Umbilical arterial blood gases and serum electrolyte and lactate concentrations were measured simultaneously in 210 samples from 63 infants over the first week of life. Metabolic acidosis was defined as a blood base deficit (BD) >4 mmol/L. The anion gap was calculated as [Na(+)] - [C1(-)] - [TCO (2)]. Lactic acidosis was defined as a serum lactate concentration >2 SD above the mean serum lactate concentration in samples without metabolic acidosis. RESULTS: In 89 blood samples with BD <4 mmol/L, serum lactate concentration decreased with postnatal age (r = 0.51). The upper limit of serum lactate concentration was 3.8 mmol/L at less than 48 hours, 2.4 mmol/L between 48 and 96 hours, and 1.5 mmol/L for infants greater than 96 hours of age. The mean serum anion gap +/- 2 SD in 174 samples without lactic acidosis was 8 +/- 4 mmol/L; in 36 samples with lactic acidosis it was 16 +/- 9 mmol/L (P <.0001). Serum anion gap and lactate concentration were poorly correlated for samples without lactic acidosis (r = 0.04) but highly correlated in those with lactic acidosis (r = 0.81, P <.0001). None of the 85 samples with metabolic acidosis but without lactic acidosis had an anion gap >16 mmol/L; only 4 of 36 samples with lactic acidosis had an anion gap <8 meq/L. However, 25 of 36 samples with lactic acidosis had serum anion gaps of 8 to 16 mmol/L. CONCLUSION: In the presence of metabolic acidosis, a serum anion gap >16 mmol/L is highly predictive of lactic acidosis; a serum anion gap <8 is highly predictive of the absence of lactic acidosis; an anion gap = 8 - 16 mmol/L has no use in the differential diagnosis of metabolic acidosis in the critically ill newborn.     

The relationship between blood glucose and serum electrolyte levels in children with acute diarrhea.

The relationship between simultaneous serum electrolyte and blood glucose levels was studied in 119 moderately or severely dehydrated children with acute infectious gastroenteritis. Their ages ranged between two months to fifteen years. A positive correlation was found between blood glucose and serum sodium levels in the children with serum bicarbonate values below 15 mmol/L. This correlation is more prominent in cases of severe metabolic acidosis with serum bicarbonate values less than 10 mmol/L. No correlation was found between blood glucose, serum potassium and chloride levels. Our results show that a positive correlation between blood glucose and serum sodium levels is present only in cases with metabolic acidosis, which is contrary to classical knowledge.     

Randomised controlled trial of intravenous maintenance fluids

Aim:   Traditional paediatric intravenous maintenance fluids are prescribed using hypotonic fluids and the weight-based 4:2:1 formula for administration rate. However, this may cause hyponatraemia in sick and post-operative children. We studied the effect of two types of intravenous maintenance fluid and two administration rates on plasma sodium concentration in intensive care patients.
Methods:   A Factorial-design, double-blind, randomised controlled trial was used. We randomised 50 children with normal electrolytes without hypoglycaemia who needed intravenous maintenance fluids for >12 h to 0.9% saline (normal saline) or 4% dextrose and 0.18% saline (dextrose saline), at either the traditional maintenance fluid rate or 2/3 of that rate. The main outcome measure was change in plasma sodium from admission to 12–24 h later.
Results:   Fifty patients (37 surgical) were enrolled. Plasma sodium fell in all groups: mean fall 2.3 (standard deviation 4.0) mmol/L. Fluid type ( P  = 0.0063) but not rate ( P  = 0.12) was significantly associated with fall in plasma sodium. Dextrose saline produced a greater fall in plasma sodium than normal saline: difference 3.0, 95% confidence interval 0.8–5.1 mmol/L. Full maintenance rate produced a greater fall in plasma sodium than restricted rate, but the difference was small and non-significant: 1.6 (−0.7, 3.9) mmol/L. Fluid type, but not rate, remained significant after adjustment for surgical status. One patient, receiving normal saline at restricted rate, developed asymptomatic hypoglycaemia.
Conclusion:   Sick and post-operative children given dextrose saline at traditional maintenance rates are at risk of hyponatraemia.     

Acid base balance in blood and cerebrospinal fluid.

Thirty four infants were studied; 21 with acute gastroenteritis, dehydration, and metabolic acidosis and 13 who served as controls. All infants with metabolic acidosis and without neurological signs had a normal to near normal cerebrospinal fluid acid base balance, but five with metabolic acidosis and severe neurological signs had cerebrospinal fluid acid base disequilibrium. Acute metabolic acidosis in infants may lead to cerebrospinal fluid acid base imbalance causing cerebral dysfunction.