Guidelines for the treatment of acidaemia with THAM.

THAM (trometamol; tris-hydroxymethyl aminomethane) is a biologically inert amino alcohol of low toxicity, which buffers carbon dioxide and acids in vitro and in vivo. At 37 degrees C, the pK (the pH at which the weak conjugate acid or base in the solution is 50% ionised) of THAM is 7.8, making it a more effective buffer than bicarbonate in the physiological range of blood pH. THAM is a proton acceptor with a stoichiometric equivalence of titrating 1 proton per molecule. In vivo, THAM supplements the buffering capacity of the blood bicarbonate system, accepting a proton, generating bicarbonate and decreasing the partial pressure of carbon dioxide in arterial blood (paCO2). It rapidly distributes through the extracellular space and slowly penetrates the intracellular space, except for erythrocytes and hepatocytes, and it is excreted by the kidney in its protonated form at a rate that slightly exceeds creatinine clearance. Unlike bicarbonate, which requires an open system for carbon dioxide elimination in order to exert its buffering effect, THAM is effective in a closed or semiclosed system, and maintains its buffering power in the presence of hypothermia. THAM rapidly restores pH and acid-base regulation in acidaemia caused by carbon dioxide retention or metabolic acid accumulation, which have the potential to impair organ function. Tissue irritation and venous thrombosis at the site of administration occurs with THAM base (pH 10.4) administered through a peripheral or umbilical vein: THAM acetate 0.3 mol/L (pH 8.6) is well tolerated, does not cause tissue or venous irritation and is the only formulation available in the US. In large doses, THAM may induce respiratory depression and hypoglycaemia, which will require ventilatory assistance and glucose administration. The initial loading dose of THAM acetate 0.3 mol/L in the treatment of acidaemia may be estimated as follows: THAM (ml of 0.3 mol/L solution) = lean body-weight (kg) x base deficit (mmol/L). The maximum daily dose is 15 mmol/kg for an adult (3.5L of a 0.3 mol/L solution in a 70kg patient). When disturbances result in severe hypercapnic or metabolic acidaemia, which overwhelms the capacity of normal pH homeostatic mechanisms (pH < or = 7.20), the use of THAM within a 'therapeutic window' is an effective therapy. It may restore the pH of the internal milieu, thus permitting the homeostatic mechanisms of acid-base regulation to assume their normal function. In the treatment of respiratory failure, THAM has been used in conjunction with hypothermia and controlled hypercapnia. Other indications are diabetic or renal acidosis, salicylate or barbiturate intoxication, and increased intracranial pressure associated with cerebral trauma. THAM is also used in cardioplegic solutions, during liver transplantation and for chemolysis of renal calculi. THAM administration must follow established guidelines, along with concurrent monitoring of acid-base status (blood gas analysis), ventilation, and plasma electrolytes and glucose.

Orofacial herpes simplex virus infection in hairless mice: latent virus in trigeminal ganglia after topical antiviral treatment.

Inoculation of herpes simplex virus on the forehead and/or snout of hairless mice resulted in a significantly lower mortality rate than inoculation of the skin in the lumbosacral area. Latent herpes simplex virus infections were detected in all forehead-inoculated and in 90% of snout-inoculated mice. Phosphonoacetic acid was highly effective in preventing the development of skin lesions, and no latent infections were detected when phosphonoacetic acid ointment was applied 3 h after infection. Neither adenine arabinoside nor adenine arabinoside monophosphate prevented the establishment of latent infections in the trigeminal ganglia, although they protected the mice from the fatal outcome of the infection. The antibody response after adenine arabinoside or adenine arabinoside monophosphate treatment was similar to that observed in untreated animals, and it was six to eight times higher than in mice treated with phosphonoacetic acid. Mice without evidence of latent infection had, in general, lower serum antibody titers than those with latent infections in the ganglia. An analysis of the pathogenesis of herpes simplex virus infection in mice treated with adenine arabinoside showed that virus penetration into the nerve endings was delayed and that the amount of free virus in ganglionic homogenates was 10 to 100 times less than that for untreated mice.

Effect of magnesium sulfate on the development of cystic periventricular leukomalacia in preterm infants.

To determine if magnesium sulfate has an effect on the development of cystic periventricular leukomalacia in preterm infants, this retrospective case control study was conducted. There were 23,382 infants born at three teaching hospitals in the metropolitan New York area from January 1992 to December 1994. Four hundred ninety-two infants met our entrance criteria. Criteria included a birth weight < 1750 g, survival to at least 7 days of life and at least one cranial ultrasound after 7 days of life. Infants exposed to magnesium sulfate in utero were less likely to develop periventricular leukomalacia. Two of 18 (11%) infants with periventricular leukomalacia were exposed to magnesium sulfate in-utero compared to 14 of 36 controls (39%) (p = 0.035) (OR = 0.196, 95% CI = 0.039-0.988). Pre-eclampsia as an independent factor was not associated with a reduced risk (p = 0.251) (OR = 0.294, 95% CI = 0.033-2.65). Preterm infants exposed to antenatal magnesium sulfate were found to have a reduced risk of developing cystic periventricular leukomalacia.