Counting unplanned extubations: marked variation among neonatologists.

OBJECTIVE: To assess if neonatologists detect and count unplanned extubations (UEs) uniformly. STUDY DESIGN: An Institutional Review Board-exempted anonymous web-based survey of neonatology attending and fellow members of the AAP Neonatal-Perinatal Medicine section was administered. Respondents were queried on practices concerning UE; they were then presented with different case scenarios and asked if they would count the event as a UE. RESULTS: Of the 509 respondents, 61% track UE rates. Of those who track UE rates, 53% reported rates of 1-3 per 100 ventilator days. The top two factors perceived as causing UEs were endotracheal tube (ETT) dislodgement by patient (65%) and failure of ETT holding system at attachment to the face (56%). In the various scenarios where ETT was urgently removed by staff, only 19 to 62% of respondents counted the event as a UE, including 23% if the ETT was removed by the attending. There was consensus on the scenarios representing self-extubation and elective change of the ETT. CONCLUSIONS: There is wide variation in methods for detecting and counting UE events among neonatologists, which precludes comparison of UE rates across institutions. We speculate that a standardized definition and classification of events will enable benchmarking among neonatal intensive care units, which should accelerate collaborative improvement efforts towards reducing UEs in neonates.

Randomized trial of laryngeal mask airway versus endotracheal intubation for surfactant delivery.

OBJECTIVE: To compare the effectiveness of surfactant delivery via endotracheal tube (ETT) using an intubation-surfactant-rapid extubation approach with premedication) vs laryngeal mask airway (LMA) in preventing the need for mechanical ventilation in preterm neonates with moderate respiratory distress syndrome (RDS). STUDY DESIGN: Moderately preterm infants diagnosed with RDS, receiving nasal continuous positive airway pressure with FiO2 0.30 to 0.60, were randomized to two groups at age 3 to 48 h. Those in the ETT group were intubated following premedication with atropine and morphine, whereas the LMA group received only atropine. Both groups received calfactant before a planned reinstitution of nasal continuous positive airway pressure, and had equivalent pre-specified criteria for subsequent mechanical ventilation and surfactant retreatment. The primary outcome was failure of surfactant treatment strategy to avoid mechanical ventilation; we differentiated early from late failures to assess the contribution of potential mechanisms such as respiratory depression versus less-effective surfactant delivery. Secondary outcomes addressed efficacy and safety end points. RESULT: Sixty-one patients were randomized, one excluded and 30 analyzed in each group, with similar baseline characteristics. Failure rate was 77% in the ETT group and 30% in the LMA group (P<0.001). The difference was related to early failure, as late failure rates did not differ between groups. FiO2 decrease after surfactant and rates of adverse events were similar between groups. CONCLUSION: Surfactant therapy through an LMA decreases the proportion of newborns with moderate RDS who require mechanical ventilation, when compared with a standard endotracheal intubation procedure with sedation. The efficacy of surfactant in decreasing RDS severity appears similar with both methods. Morphine premedication likely contributed to early post-surfactant failures.

The concordance of ultrasound technique versus X-ray to confirm endotracheal tube position in neonates.

OBJECTIVE: Given the distressingly high incidence of ETT malposition in the neonatal population, patients are exposed to ionizing radiation to confirm endotracheal tube (ETT) position. Our objective is to determine if ultrasound technique is concordant with X-ray in determining whether an ETT is deeply positioned or not. STUDY DESIGN: Prospective observational clinical trial. After obtaining informed consent, patients with an ETT who required X-ray for clinical reasons underwent sonographic evaluation of the ETT by an ultrasound technologist or pediatric radiologist, usually within the hour. RESULTS: A total of 56 image pairs were obtained from 29 patients. Ninety-eight percent of the ultrasound/X-ray image pairs were suitable for analysis. The concordance of ultrasound with X-ray to identify deeply and not deeply positioned ETTs was 95% (53/56). The sensitivity of ultrasound to detect deeply positioned ETTs on X-ray was 86% (6/7). The specificity of ultrasound to detect ETTs that were not deeply positioned on X-ray was 96% (47/49). CONCLUSIONS: As the largest clinical trial of its kind to date, with the greatest number of ultrasound operators, we have further established US as a feasible imaging modality to determine whether an ETT is deeply positioned or not.

Role of local anesthesia during lumbar puncture in neonates.

Local anesthesia decreases physiologic responses to pain in neonates but has not been used routinely during lumbar punctures in newborns, as it might obscure anatomical landmarks. However, local anesthesia may decrease newborns' struggling during lumbar puncture, thus facilitating the procedure and increasing its success rate. The success rate of lumbar punctures was compared in neonates allocated prospectively to 0.2 to 0.5 mL of 1% lidocaine anesthesia (n = 48) or a control group (n = 52). Newborns were held in a modified lateral recumbent position (neck not flexed) and their struggling response to the various steps in the lumbar puncture was scored by the holder. The newborns' struggling motion score increased in response to lidocaine injection, but response to the subsequent spinal needle insertion was significantly decreased. Despite this decreased motion, no differences were noted in the number of attempts per lumbar puncture (1.9 +/- 0.2 [SEM] in lidocaine and 2.1 +/- 0.2 in control groups), rate of lumbar puncture failure (15% in lidocaine and 19% in control groups), or the number of traumatic lumbar punctures (46% in both groups). The success rate of lumbar puncture was not dependent on level of training of physicians performing the procedure. No acute complications, cerebrospinal fluid contamination, or subsequent meningitis was noted in either group. It is concluded that local anesthesia with lidocaine decreases the degree of struggling but does not alter the success rate of lumbar puncture in neonates. The practice of withholding lidocaine anesthesia from neonates undergoing lumbar punctures cannot be justified by arguing that it makes the procedure more difficult to perform.

Detection of endothelin-like immunoreactivity in epithelium and fibroblasts of the human umbilical cord.

We studied tissue sections of freshly obtained full-term and premature human umbilical cords using polyclonal antibody to endothelin and immunocytochemistry. Endothelin immunoreactivity was detected in the cytoplasm of epithelial cells and primitive fibroblasts, but not in the endothelial cells of both full-term and premature umbilical cords. Immunoelectron microscopy using indirect immunogold staining technique localized endothelin immunoreactivity to the cytoplasm of the epithelial cells and fibroblasts but not confined to any particular structures. No endothelin immunoreactivity was detected in the nucleus or on the cell membrane. Pre-absorption tests with synthetic endothelin-1, -2, and -3 independently established that the immunoreactivity represented endothelin-1 and -2, but not -3. The presence of endothelin-1 and -2-like immunoreactive materials in epithelial cells and fibroblasts of human umbilical cord suggests a role of endothelin in parturition.

[Renal colic]. / Cólica renal.

The appropriate approach to renal colic, which should be known by the family doctor, is presented. The incidence of this condition in the emergency department of a large general hospital is described as well as the physiopathology of pain, its clinical aspects and the therapeutic attitudes. Renal colic is frequent, it is often possible to diagnose the clinical aspects and general practitioners have the competence for treatment. The use of analgesic drugs, in the correct dosage, is enough to relieve pain and suffering in most of the patients.

Facile synthesis of oxo-/thioxopyrimidines and tetrazoles C-C linked to sugars as novel non-toxic antioxidant acetylcholinesterase inhibitors.

Microwave-assisted synthesis of oxo-/thioxopyrimidines and tetrazoles linked to furanoses with D-xylo and D-ribo configuration, and to a D-galacto pyranose is reported and compared to conventional methods. Reaction of dialdofuranoses and dialdopyranoses with a ß-keto ester and urea or thiourea under microwave irradiation at 300 W gave in 10 min the target molecules containing the 2-oxo- or 2-thioxo-pyrimidine ring in high yield. The tetrazole-derived compounds were obtained in two steps by reaction of the formyl group with hydroxylamine hydrochloride, copper sulfate, triethylamine and dicyclohexylcarbodiimide to give an intermediate nitrile, which was then treated with sodium azide. The use of microwave irradiation in the latter step also resulted in a considerably shorter reaction time (10 min) compared to hours under conventional heating to obtain a complete starting materials conversion. Acetylcholinesterase inhibition ranged from 20% to 80% for compounds concentration of 100 µg/mL, demonstrating the potential of this family of compounds for the control of Alzheimer's disease symptoms. Most of the compounds showed antioxidant activity in the ß-carotene/linoleic acid assay, some of them exhibiting IC(50) values in the same order of magnitude as those of gallic acid. The bioactive compounds did not show cytotoxic effects to human lymphocytes using the MTT method adapted for non-adherent cells, nor genotoxicity determined by the short-term in vitro chromosomal aberration assay.

The Apgar cycle: a new view of a familiar scoring system.

Apgar scores are universally recorded, but they should no longer be used to guide resuscitation; thus, some authorities have suggested that the scores should be abandoned. However, the physiological relationships underlying the elements of the Apgar scoring system can be conceptualised as a cycle, wherein the five functions are linked by cardiorespiratory reflexes and metabolically supported by the oxygen pathway. Respiratory effort represents both the main input into the system and its functional output (sustained respirations). The progressive deterioration of functions during asphyxia, and their recovery during resuscitation, are readily understood within the sequence. This depiction helps in learning concepts such as primary and secondary apnoea and bradycardia. The visual model harmonises the pedagogical and practical values of the Apgar scoring system, by placing the rapid assessment of respirations, heart rate and colour during neonatal resuscitation (as taught in the Neonatal Resuscitation Program) in its broader physiological context. The understanding imparted by the Apgar cycle may directly enhance patient care during resuscitation, apart from the attribution of numerical scores.

Mechanisms of endothelin-1-induced pulmonary vasodilatation in neonatal pigs.

1. We determined the contributions of three independent vasodilator mechanisms (cyclo-oxygenase metabolites, nitric oxide and ATP-sensitive potassium channels) in the mediation of pulmonary vasomotor effects of endothelin-1 (ET-1) in neonatal pigs. 2. Lungs of piglets (2.7 +/- 0.3 days old) were perfused at constant flow (60 ml min-1) with recirculating Ringer-albumin solution. We measured pulmonary artery pressure (Ppa) and the distribution of pulmonary vascular resistance using the double-occlusion method. 3. ET-1 (10(-12)-10(-9) M) produced concentration-dependent pulmonary vasodilatation. ET-1 (10(-9) M) decreased Ppa from 24.5 +/- 3.1 to 17.0 +/- 3.0 cmH2O with a nadir occurring at 1 min, followed by a slow return to baseline over 60 min (time for half-recovery (t1/2R) of 17.2 min). The decrease in Ppa was the result of pulmonary precapillary vasodilatation. Endothelin-3 (ET-3) (10(-12) and 10(-11) M) also induced vasodilatation comparable to equimolar concentrations of ET-1, whereas the selective ETB receptor agonist IRL 1620 at equimolar concentrations caused a more protracted vasodilatation response. 4. Neither the cyclo-oxygenase inhibitor indomethacin (10(-5) M) nor the KATP+ (ATP-sensitive) potassium channel blocker glibenclamide (10(-5) M) significantly altered the baseline Ppa; moreover, neither inhibitor affected the ET-1-induced vasodilatation, indicating the lack of involvement of cyclo-oxygenase metabolites and KATP+ channel activity in the mediation of the pulmonary vasodilator response to ET-1. 5. Addition of 10(-5) M reduced haemoglobin, which antagonizes the action of nitric oxide (NO), increased Ppa over prehaemoglobin levels. Haemoglobin significantly decreased the duration (t1/2R, 3.8 +/- 0.7 min) of pulmonary vasodilatation to ET-1, but did not abolish the initial phase of the response. L-N-Monomethylarginine, an inhibitor of NO synthesis, either alone or in combination with haemoglobin, similarly reduced the duration of ET-1-induced pulmonary vasodilatation. 6. The ETA receptor antagonist [Dpr1-Asp15]-ET-1 (Dpr, diaminoproprionic acid) had no effect on pulmonary vasodilatation induced by ET-1, ET-3 or IRL 1620 (suc-(Glu9,Ala11,15)-ET-1(8-21)). This finding combined with the observed relative potencies of the peptides (IRL 1620 > ET-1 = ET-3) suggests that pulmonary vasodilatation was mediated by activation of the non-selective ETB receptor. 7. The results indicate that the sustained ET-1-induced pulmonary vasodilatation in neonates is probably mediated via ETB receptor activation and that it is critically dependent on NO.

K+ATP-channel activation causes marked vasodilation in the hypertensive neonatal pig lung.

We studied the potential role of ATP-sensitive potassium (K+ATP) channel activation in mediating pulmonary vasodilation in newborn piglets. Piglet lungs (n = 14, ages 1-4 days) were artificially perfused with recirculating Ringer solution containing bovine serum albumin and statistically inflated using 95% O2-5% CO2. We measured pulmonary arterial pressure (Ppa) and distribution of pulmonary vascular resistance (using double-occlusion method). Under resting conditions (Ppa 13.7 +/- 1.6 cmH2O, mean +/- SE), the K+ATP channel agonist BRL 38227 (lemakalim, 10(-7) and 10(-6) M) caused small dose-dependent pulmonary vasodilation. This response was diminished by the K+ATP-channel blocker glibenclamide (10(-5) M). Pretreatment of lungs with indomethacin (10(-5) M) and N omega-nitro-L-arginine (10(-5) M) to inhibit cyclooxygenase- and nitric oxide (NO)-related vasodilation, respectively, resulted in a marked increase in the baseline Ppa to 85.6 +/- 11.2 cmH2O. Injection of BRL 38227 (10(-7) M and 10(-6) M) in these lungs decreased Ppa to 72.5 +/- 8.5 (P < 0.01) and 19.3 +/- 0.9 cmH2O (P < 0.01), respectively; the corresponding times for half-recovery of Ppa (t1/2R) were 5.7 +/- 4.3 and > 20 min. Glibenclamide (10(-5) M) abolished the response to 10(-7) M BRL 38227 and significantly diminished (P < 0.05) the decreases in Ppa and t1/2R in response to 10(-6) M BRL 38227 but not to acetylcholine (10(-10) M). We conclude that activation of K+ATP channels has a minimal role in maintaining basal pulmonary vasomotor tone but is able to induce marked vasodilation when NO and cyclooxygenase-dependent vasodilatory mechanisms are inhibited.

Use of a triple-lumen catheter for umbilical venous access in the neonate.

We describe the use of a triple-lumen catheter inserted through the umbilical vein for infusion of vasoactive substances, fluids, and blood products, and also for withdrawal and exchange transfusion of blood and central venous pressure monitoring. Catheter malfunction occurred in 5 of 16 cases and was related to leaks or inability to draw blood via the desired port. No complications were attributable to catheter insertion or use.

Receptor mechanism of thrombin-mediated pulmonary vasodilation in neonates.

A recently identified peptide sequence exposed after proteolytic cleavage of the NH2-terminus of the thrombin receptor mimics some cellular effects of alpha-thrombin. To determine whether a proteolytic action of thrombin is required for vasoactivity, we examined the vascular effects of modified thrombins and synthetic NH2-terminus peptide sequences of the thrombin receptor (TRPs) in isolated piglet lungs. Lungs of piglets 1-6 days old were perfused with recirculating Ringer-albumin solution at a constant flow of 60 ml/min. We measured the pulmonary artery pressure (Ppa) and segmental distribution of pulmonary vascular resistance (using the double occlusion method) in response to injections of human alpha-thrombin, modified thrombins, and TRP-14 and TRP-7 (i.e., 14 and 7 amino acid NH2-terminus peptides of the cleaved thrombin receptor). alpha-Thrombin produced a rapid and transient decrease in Ppa; the magnitude and duration [time for one-half recovery (t1/2 R)] of the vasodilation responses were concentration dependent [t1/2 R values of 1.4 +/- 0.1 and 3.3 +/- 2.4 min (mean +/- SE) at concentrations of 10(-10) and 10(-9) M, respectively]. The vasodilation was due primarily to a decrease in precapillary resistance. Proteolytically active, but binding-impaired gamma-thrombin was a less potent vasodilator and proteolytically inactive D-phenylalanyl-prolyl-arginine-chloromethyl ketone (PPACK)-alpha-thrombin did not induce vasodilation. TRP-14 was also a pulmonary vasodilator with a t1/2R value of 0.8 +/- 0.09 min at a concentration of 10(-7) M; both TRP-14 and TRP-7 were approximately 3-log less potent than equimolar alpha-thrombin.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of endothelin-1-induced pulmonary vasoconstriction.

Endothelins are endothelial cell-derived peptides with potent vasoconstrictor properties. We investigated the actions of porcine/human endothelin-1 (ET-1) on the microvasculature of the guinea pig lung perfused at constant flow with Ringers-albumin. We measured the perfusion pressure, distribution of pulmonary vascular resistance (using the double occlusion method), lung weight change, and the pulmonary capillary filtration coefficient. At concentrations of greater than or equal to 10(-10) M, ET-1 produced dose-dependent increases in mean pulmonary artery pressure (EC50, approximately 10(-9.5) M), which were rapid in onset and biphasic (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) up to 60 minutes of the perfusion period. The vasoconstrictor response was sustained for the 60-minute perfusion period. The pulmonary vasoconstriction was inhibited by pretreatment with indomethacin (10(-5) M), the thromboxane A2 receptor antagonist SQ-29,548 (4 x 10(-6) M), or papaverine (10(-5) M). Nifedipine (10(-5) or 10(-7) M) had no effect on the first phase but prevented the second phase of the vasoconstriction. The vasoconstriction was primarily the result of a 10-fold increase in pulmonary venous resistance. Pulmonary edema developed after ET-1 challenge because of the venoconstriction and the resultant pulmonary capillary hypertension. However, the pulmonary capillary filtration coefficient was unchanged, indicating that pulmonary vascular permeability did not increase. ET-1 also had no effect on transendothelial 125I-albumin flux. The results indicate that ET-1 is a potent thromboxane-dependent venoconstrictor in the guinea pig lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of platelet-activating factor and thromboxane in group B Streptococcus-induced pulmonary hypertension in piglets.

Platelet-activating factor causes pulmonary hypertension, shock, hypoxemia, neutropenia, and increased pulmonary vascular permeability; some of its effects are due to thromboxane A2 release. Evidence for a possible role of these mediators in the genesis of group B Streptococcus (GBS)-induced pulmonary hypertension was sought using specific receptor antagonists for PAF and thromboxane A2 (TxA2) in anesthetized, ventilated piglets (less than or equal to 12 d of age; n = 22). Infusion of 1 X 10(8) GBS/kg/min for one hour resulted in a sustained and significant increase in pulmonary artery pressure (PPA) from 17 +/- 1 to 35 +/- 3 torr. Pretreatment with the TxA2 antagonist SQ 29548 (0.75 mg/kg intravenous), completely inhibited the effect of GBS on PPA. Pretreatment with either platelet-activating factor antagonists SRI 63072 (3 mg/kg intravenous) or SRI 63441 (1 mg/kg) did not affect the pulmonary hypertension due to GBS infusion. GBS-induced pulmonary hypertension could be reversed by SQ 29548; SRI 63072 did not affect PPA when administered to pigs with GBS-induced elevation in PPA. Inasmuch as prevention and reversal of GBS-induced pulmonary hypertension are accomplished with the TxA2 antagonist but not with PAF antagonists, these data suggest that TxA2, rather than PAF, is responsible for the early pulmonary hypertension in this model of neonatal GBS sepsis. Therefore, TxA2 antagonists may be clinically useful in treating pulmonary hypertension related to GBS sepsis.

Growth characteristics of pulmonary artery smooth muscle cells from fawn-hooded rats.

We compared the proliferative rates of vascular smooth muscle cells (VSMC) from pulmonary arteries of pulmonary hypertensive fawn-hooded rats (FHR) with VSMC from normotensive Sprague-Dawley rats (SDR). VSMC from FHR grew at increased rates and reached higher densities at all serum concentrations studied (5-20%) than the VSMC from SDR. The VSMC from FHR also responded to epidermal growth factor (EGF) at low serum concentrations, as evidenced by significantly greater DNA synthetic rates, than the control VSMC. The increased growth in these cells could be due to increased number and/or affinity of EGF receptors because of the higher specific binding of 125I-EGF to the VSMC from FHR. The VSMC from FHR and SDR were equally sensitive to the antiproliferative effects of heparin, suggesting that the heparin-sensitive pathways are not altered in the VSMC from FHR. These results suggest that the development of pulmonary hypertension in FHR may be related to the higher proliferative capacity of the pulmonary VSMC, which may be coupled to increased activity of the EGF receptors on these cells.

Aspectos clínicos e de laboratório de cães soropositivos para leishmaniose / Clinical and laboratorial aspects of seropositive dogs to leishmaniosis

Leihsmaniasis is a protozoal disease transmitted by dipteran insects. The dog is an important domestic host of both visceral and cutaneous forms of the disease. These forms affects humans in many countries, and it is considered a serious risk for human health. This study reports clinical and laboratorial data from 18 dogs. Nine dogs were positive by indirect immunofluorescence technique and the other nine were negative. The dogs were clinically monitored for 30 days and laboratorial changes were assessed. Three blood samples were collected for hemogram and serum biochemistry at 0, 15, and 30 days. The clinical signs of positive dogs were compatible with the disease, including lymphadenopathy, cutaneous ulcers, hyperthermia, apathy, cachexia and ulcerated mucosa. Marked differences were observed in the blood cell counts and blood biochemistry between positive and negative dogs. In conclusion, blood and biochemistry analyses of positive dogs were not sufficient to diagnose the disease within the period studied. The serologic test associated with the clinical signs are important to confirm the diagnosis.

Avaliacao de acetaminofen, dipirona e placebo no tratamento da dor pos-amigdalectomia. / Evaluation of acetaminophen, dipyrone and placebo in the treatment from post-tonsillectomy pain

Estudou-se, de forma duplo-cega, a eficacia analgesica e tolerancia a administracao de dose unica de acetaminofen (500 mg) dipirona (500 mg) e placebo em 85 pacientes com dor subsequente a amigdalectomia.Os grupos se caracterizaram pela homogeneidade dos parametros demograficos no pre-tratamento (hora mais elevada, em comparacao aos grupos dipirona e placebo. Durante as quatro horas de duracao do estudo avaliou-se a eficacia dos tratamentos pela analise dos escores de intensidade da dor (0 = ausente; 1 = leve; 2 = moderado e 3 = intensa), e alivio da dor (0 = nenhum; 1 = pequeno; 2 = moderado; 3 = acentuado e 4 = completo). Estes itens permitiram obter-se parametros indiretos: DID = diferenca de intensidade da dor a cada avaliacao em relacao a dor inicial; MAXDID: diferenca maxima de intensidade da dor; SDID: soma das diferencas de intensidade da dor; TOT-AL: maximo alivio obtido nas quatro horas de avaliacao. Tambem considerou-se a necessidade de analgesico suplementar e a eventual ocorrencia de reacoes adversas aos tratamentos. Durante as cinco avaliacoes, apos a administracao dos medicamentos (30 minutos, 1a., 2a., 3a. e 4a. horas) a analise dos parametros mencionados revelou equipotencia analgesica do acetaminofen em relacao a dipirona, ambos se mostrando estatisticamente superiores ao placebo.A tolerabilidade as drogas foi considerada excelente