A comparison of the effects of hydromorphone HCl and a novel extended release hydromorphone on arterial blood gas values in conscious healthy dogs.

The purpose of this study was to evaluate arterial blood gases in dogs that were given hydromorphone or extended release liposome-encapsulated hydromorphone (LEH). Dogs were randomly administered LEH, n=6, (2.0 mg kg(-1)), hydromorphone, n=6, (0.2 mg kg(-1)) or a placebo of blank liposomes, n=3, subcutaneously on separate occasions. Arterial blood samples were drawn at serial time points over a 6-h time period for blood gas analysis. There was no change from baseline values in P(a)CO(2), P(a)O(2), (HCO(3)-), pH, and SBEc in the dogs that received the placebo. Administration of hydromorphone resulted in significant increases in P(a)CO(2) (maximum (mean+SD] 44.4+1.1mm of Hg) and significant decreases in P(a)O(2) (minimum (mean+SD) 82.4+4.7 mm of Hg) and pH (minimum (mean+SD) 7.31+0.01) compared with baseline. Administration of LEH resulted in significant increases in P(a)CO(2) (maximum (mean+SD) 44.6+0.9 mm of Hg) and significant decreases in P(a)O(2) (minimum (mean+SD) 84.8+2.6mm of Hg) and pH (minimum (mean+SD) 7.34+0.02) compared with baseline. There was no significant difference between these two groups at any time point. The changes observed in P(a)CO(2), P(a)O(2), and pH, however, were within clinically acceptable limits for healthy dogs. LEH was determined to cause moderate changes in arterial blood gas values similar to those caused by hydromorphone.

Antithrombin III deficiency in neonatal respiratory distress syndrome.

Neonatal respiratory distress syndrome (RDS) is an acute lung injury believed to result primarily from surfactant deficiency in the immature lung. Although surfactant replacement therapy has improved the outcome of this disease, RDS remains a major cause of neonatal mortality and morbidity. Preliminary experimental evidence suggests that unopposed intravascular thrombin activity may contribute to the progression of RDS by promoting high permeability pulmonary oedema and pulmonary hypertension. In the extravascular lung compartment, polymerizing fibrin may inhibit surfactant function. In addition, interstitial and alveolar thrombin formation and resulting fibrin deposition may contribute to the development of chronic lung disease through amplification of inflammation and fibrosis. There is good evidence that extravascular coagulation occurs during the course of RDS. Fibrin is a major component of the hyaline membranes, which are a hallmark of acute lung injury, and which can be regarded as locally produced clots. It has been less certain whether neonatal RDS is also associated with intravascular activation of the coagulation system. Although low levels of antithrombin III (AT III) have been reported in infants with RDS, direct evidence of increased intravascular thrombin formation has been lacking. However, recently, plasma concentrations of thrombin-antithrombin III (TAT) complexes have been measured in infants with RDS and correlated with RDS severity. TAT formation was significantly increased in severe neonatal RDS, while free AT III activity was decreased. These data are consistent with increased thrombin generation and resulting AT III consumption. Therefore, to regulate thrombin activity, infants with severe RDS may benefit from replacement therapy with AT III concentrate. This hypothesis has been strengthened by experiments that have demonstrated the efficacy of thrombin inhibition in several animal models of acute lung injury. However, controlled clinical trials will be required to determine whether thrombin is just a coincidental marker of neonatal RDS, or whether unopposed thrombin activity exacerbates the disease process.

Coagulation screening tests in high risk neonates: a prospective cohort study.

Forty seven infants in a prospective cohort of 170 high risk neonates without signs of overt bleeding had abnormal coagulation screening tests within 36 hours of birth. Early thrombocytopenia was a better predictor of prolonged prothrombin times and hypofibrinogenemia than very low birth weight, fetal growth retardation, or poor five minute Apgar scores.

An endemic strain of Staphylococcus haemolyticus colonizing and causing bacteremia in neonatal intensive care unit patients.

Coagulase-negative staphylococci are now the major cause of bacteremia in neonatal intensive care units. To date, coagulase-negative staphylococci causing neonatal infections have been found to be distinct when typed by standard techniques. To determine whether or not an endemic strain could be identified using more discriminatory techniques, we characterized coagulase-negative staphylococci isolates obtained from a prospective study of coagulase-negative staphylococci bacteremia in a neonatal intensive care unit during 1984 through 1985, by standard techniques supplemented with DNA-DNA hybridization and restriction endonuclease analysis. We typed 58 strains that were isolated from 52 episodes of bacteremia in 38 neonates. There were 46 isolates of Staphylococcus epidermidis. Three pairs of strains were identical, and each strain was from a different patient. There were 12 isolates of Staphylococcus haemolyticus. Ten were identical, referred to as strain TOR-35, and had been isolated from eight different infants. Characterization of strains obtained in 1986 from a prospective study of coagulase-negative staphylococci-colonizing neonates admitted to the same neonatal intensive care unit found the TOR-35 strain had colonized 6 of 17 neonates by day seven. A point prevalence survey of all neonates in the same neonatal intensive care unit in 1990 found 5 of 30 neonates to be colonized with the TOR-35 strain. Therefore, we were able to identify an endemic strain of S haemolyticus that caused multiple episodes of bacteremia during a 6-month period and remained present in the same environment for a 5-year period.

Coagulase-negative staphylococci as true pathogens in newborn infants: a cohort study.

We examined the pathogenicity of coagulase-negative staphylococci (CONS) in newborn infants by comparing presenting nonspecific signs of infection in infants with and without CONS bacteremia. During a 6-month period 799 blood cultures were obtained in a tertiary care nursery; 81 (10.1%) grew CONS and 25 (3.0%) grew other bacteria. A comparison group of 121 infants was selected randomly from ill patients whose blood cultures were negative. In addition 70 well infants were matched to CONS-positive cases. Abnormal clinical signs, complete blood cell counts, C-reactive protein, alpha-1-acid glycoprotein and prealbumin were determined at the time of culture. Signs that discriminated best between infants with and without CONS bacteremia were identified by logistic regression analysis. Infants with CONS bacteremia did not differ from infants with sepsis caused by recognized pathogens, except for lethargy, which was significantly more common in unequivocal infection. Infants with presumed infection but negative blood cultures, and noninfected control patients had abnormal signs significantly less often than CONS-positive infants. C-reactive protein, hyperthermia, increased oxygen requirements and lethargy were the most useful signs in identifying neonatal bloodstream infection. This cohort study provides objective evidence for the pathogenicity of CONS in newborn infants.

Low antithrombin III in neonatal shock: DIC or non-specific protein depletion?

Low antithrombin III (AT III) levels in shock are usually ascribed to disseminated intravascular coagulation (DIC). However, decreased activities of clotting factors and their inhibitors could reflect a generalised fall in plasma proteins rather than DIC. AT III and albumin were compared in 48 asphyxiated and non-asphyxiated newborn rabbits (pH 6.70-7.30). Both AT III and albumin were markedly decreased in the sickest animals and there was a direct linear relationship between the two proteins (P less than 0.001). Similar results were obtained in ten newborn infants suffering from shock and haemorrhagic diathesis. In all cases AT III and albumin were decreased below the normal range and significantly correlated (P less than 0.01). Our findings suggest that AT III is not a useful diagnostic marker of DIC. Further, a similar fall of clottable and non-clottable proteins in shock questions the general assumption that the ensuing coagulopathy is due to intravascular coagulation.