Phases of fluid and electrolyte homeostasis in the extremely low birth weight infant.

OBJECTIVE: We had shown previously that preterm infants undergo three phases of fluid and electrolyte homeostasis; prediuretic, diuretic, and postdiuretic. The objectives of the present study were: (1) to determine whether infants even more immature and infants cared for under thermal environmental conditions different from those previously studied also undergo these three phases; and (2) to relate these phases to changes in renal function. METHODS: Consecutive, timed urine collections were made during the first 5 days of life in 32 infants with birth weights of 1000 g or less. Infants were cared for in radiant warmers for 24 hours and then transferred to nonhumidified incubators. Diuresis was defined as urine flow rate (V) of 3 mL or more/kg per hour and weight loss of 0.8 g or more/kg per hour. The physiologic relationships among water and sodium balance, insensible water loss, arterial blood pressure, and renal function were made during the three phases. RESULTS: Twenty-eight (87%) of the 32 infants underwent the three homeostatic phases. The median ages of onset and cessation of diuresis were 25 and 96 hours, respectively. There was no correlation between onset of diuresis and change of thermal environment. During the prediuretic phase, V averaged 1.6 mL/kg per hour, and 17 of 28 infants had at least one collection period in which V was less than 1 mL/kg per hour; urinary sodium excretion was 0.1 mEq/kg per hour; the glomerular filtration rate (GFR) was 0.22 mL/kg per hour; fractional excretion of sodium (FENa) was 6.2%; and urine osmolality was dilute (221 mOsm/kg). During the diuretic phase, V and sodium excretion more than tripled; GFR and FENa doubled; and there was no change in urine osmolality. During postdiuresis, V and Na excretion decreased to values intermediate between the prediuretic and diuretic phases, and FENa fell to prediuretic levels, but there was no change in GFR or urine osmolality. There was poor correlation between blood pressure and GFR. Insensible water loss was high and variable during all phases, exceeding 190 mL/kg per day in the smallest infants. CONCLUSIONS: Extremely low birth weight infants manifest three phases of fluid and electrolyte homeostasis, as do more mature infants, independent of thermal environment. Diuresis and natriuresis are the result of abrupt increases in GFR and FENa. We speculate that this may be the result of expansion of the neonatal extracellular space as fetal lung fluid is reabsorbed.

Renal bicarbonate excretion in extremely low birth weight infants.

OBJECTIVE: To test the hypothesis that due to the immaturity of their kidneys extremely low birth weight infants lose large amounts of bicarbonate in their urine. METHODS: Urine and blood samples collected every 8 to 12 hours for the first 4 days of life from 22 preterm infants 23 to 29 weeks' gestation weighing 540 to 982 g at birth were prospectively studied. RESULTS: As described previously, three phases of fluid homeostasis were identified. The first phase (prediuresis) was a period of low urine output followed by a period of spontaneous diuresis/natriuresis (diuretic phase) and then by a phase when urine output varied according to fluid intake (postdiuresis). Sodium, potassium, chloride, and bicarbonate excretion rates and bicarbonate balance (bicarbonate or acetate infused minus bicarbonate excreted) were calculated for each of the three phases. Urinary excretion of sodium, potassium, chloride, and bicarbonate increased from the prediuretic to the diuretic phase and decreased from the diuretic to the postdiuretic phase. During the diuretic phase 88% of renal sodium excretion was accompanied by excretion of chloride. Bicarbonate balance was positive in all three fluid phases. Cumulative renal bicarbonate loss over the first 4 days of life was 1.9 +/- 0.5 meq/kg (SD) and the cumulative bicarbonate balance was +4.4 +/- 4.1 meq/kg (SD). The glomerular filtration rate, filtered load of bicarbonate, and absolute tubular reabsorption of bicarbonate significantly increased from the prediuretic to the diuretic phase, while fractional reabsorption of sodium and chloride decreased between these two phases. The fractional reabsorption of bicarbonate did not change from prediuresis to diuresis, but increased from diuresis to postdiuresis and consequently from prediuresis to postdiuresis. CONCLUSIONS: Contrary to our original hypothesis, the total renal bicarbonate excretion of extremely low birth weight infants in the first 4 days of life is low and the net bicarbonate balance is positive. The anion predominantly accompanying the excretion of sodium in all three phases is chloride and not bicarbonate. Bicarbonate excretion appears to be independent of sodium excretion during these phases. The increase in renal tubular bicarbonate reabsorption during the first week of life may be associated with extracellular volume contraction.

[Anti-arrhythmic activity of trimecaine under experimental and clinical conditions]. / Protivoaritmicheskaia aktivnost' trimekaina v eksperimente i klinike.

The antiarrhythmic properties of trimecaine, a local anesthetic, were studied. Tests on cats and rats with arrhythmia induced by stimulation with electric current and injection of aconitine, barium chloride, and calcium chloride as well as on a cell model of aconitine arrhythmia have shown that trimecaine possesses marked antiarrhythmic properties. It is more active and less toxic than procainamide hydrochloride or quinidine. Oral administration of 0.35% trimecaine solution had a favourable therapeutic effect in extrasystole in patients with complex heart valvular diseases and circulatory disorders. It is presumed that parenteral injection will produce a more rapid and prolonged antiarrhythmic effect.

Anomalous electrophoretic behavior of the membrane (M) protein of influenza virus in polyacrylamide gels.

The relative position of M and NS 1 on polyacrylamide gels depends on the concentration of cross-linker in the gel. Inversion in position of M and NS 1 occurs at a cross-linker concentration of 1.2 percent.

The membrane (M1) protein of influenza virus occurs in two forms and is a phosphoprotein.

The membrane (M1) protein of influenza virus was found to be heterogenous and to occur in two forms in the virus particle. The two forms of M1 were found in virus which was produced both early and late after infection and in infected cells. The two forms could be separated on polyacrylamide gels under specific conditions. The two components of M1 contained similar tryptic peptides. However, a small proteolytic difference between the two proteins could not be ruled out. Both M1 proteins were present in phosphorylated form in the virus particle. The phosphorylated M1 components were not readily distinguished from phosphorylated nonstructural protein (NS1) when cytoplasm of infected cells was analyzed on polyacrylamide gels. The two phosphorylated M1 components could, however, be detected in infected cells by immunoprecipitation. One M1 component contained only phosphoserine whereas the second contained phosphoserine and a small amount of phosphothreonine as well. In addition to the phosphorylated nucleoprotein and M1, a third phosphorylated protein was routinely detected in virus particles. It was a surface component of the virus, since it could be removed from whole virus with chymotrypsin and contained phosphate at serine residues. The identity of this component was not known.

Potassium metabolism in extremely low birth weight infants in the first week of life.

OBJECTIVE: Nonoliguric hyperkalemia has been reported to occur in the first week of life in as many as 50% of extremely low birth weight (ELBW) infants. We studied potassium balance and renal function in the first 5 days of life to characterize potassium metabolism during the three phases of fluid and electrolyte homeostasis that we have described in ELBW infants and to elucidate the factors that contribute to the development of nonoliguric hyperkalemia. STUDY DESIGN: Plasma potassium concentration (PK), potassium intake and output, and renal clearances were obtained for the first 6 days of life in 31 infants with a birth weight of 1000 gm or less. Collection periods in which urine flow rate was greater than or equal to 3 ml/kg per hour and weight loss was greater than or equal to 0.8 gm/kg per hour were denoted to be diuretic. Prediuresis includes all collection periods before the first diuretic period; diuresis includes all collection periods between the first and last diuretic periods; postdiuresis includes all collection periods after the last diuretic period. Infants with a PK greater than 6.7 mmol/L on at least one measurement were denoted to have hyperkalemia. RESULTS: PK increased initially after birth--despite the absence of potassium intake- and then decreased and stabilized by the fourth day of life. Diuresis occurred in 27 of 31 infants. The age at which PK peaked was closely related to the onset of diuresis. PK decreased significantly during diuresis as the result of a more negative potassium balance, despite a significant increase in potassium intake. In fact, PK fell to less than 4 mmol/L in 13 of 27 infants during diuresis. After the cessation of diuresis, potassium excretion decreased even though there was a significant increase in potassium intake, potassium balance was zero, and PK stabilized. Hyperkalemia developed in 11 of 31 infants. The pattern of change in PK with age was similar in infants with normokalemia and hyperkalemia: PK initially increased (essentially in the absence of potassium intake) and then decreased and stabilized by the fourth day of life. However, the rise in PK after birth was greater in infants with hyperkalemia than in those with normokalemia: 0.7 +/- 0.2 versus 1.8 +/- 0.2 mmol/L (p < 0.001). No differences in fluid and electrolyte homeostasis or renal function were identified as associated with hyperkalemia. CONCLUSIONS: PK increases in most ELBW infants in the first few days after birth as a result of a shift of potassium from the intracellular to the extracellular compartment. The increase in the glomerular filtration rate and in the fractional excretion of sodium, with the onset of diuresis, facilitates potassium excretion, and PK almost invariably decreases. Hyperkalemia seems to be principally the result of a greater intracellular to extracellular potassium shift immediately after birth in some ELBW infants.

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.