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Biomedical subjects

H Kirpalani

Publications and source records attributed to H Kirpalani.

At least 19 recordsLinked to original sources

Characterising doctor-parent communication in counselling for impending preterm delivery.

OBJECTIVE: To examine the counselling of women admitted to hospital in preterm labour. Such women and their partners are often asked to participate in difficult decisions including mode of delivery, fetal monitoring, and resuscitation. STUDY DESIGN: Questionnaire based descriptive study. STUDY SETTING: A tertiary level perinatal referral centre. PATIENTS: Forty-nine women in preterm labour at 22-30 weeks gestation, admitted in two separate periods between March 1997 and May 1999. INTERVENTION AND OUTCOME MEASURE: Within 24 hours of counselling, parents were asked to complete a questionnaire assessing recall of the management plan, desire for involvement in decision making, anxiety, and feelings of control over their health. A parallel questionnaire was completed by the clinicians. RESULTS: Parents and clinicians on recall agreed well about obstetric issues but poorly about neonatal issues. Overall 27% of parents felt: "I would prefer to have the doctors advise me, rather than asking me to decide". In 79% of cases, clinicians believed parents preferred advice rather than to make decisions, but in 45% of these, they misidentified those who wished to make their decisions. Anxiety levels for one third of the mothers were high, and associated with poorer concordance of recall between parents and clinicians. CONCLUSIONS: Serious deficiencies exist in parent-clinician encounters during extremely preterm labour. Concordance between parents and clinicians is poor and anxiety very high. A quarter of parents appear to prefer to relinquish decision making autonomy, but clinicians cannot correctly identify this subgroup. Standardised counselling in the perinatal period, using formal decision aids, should be investigated.

Communication↗

Neonatal brain injury.

Complacency about long-term outcomes in newborns is being eroded rapidly with new information. We have examined developments in the area from an explicitly clinical approach, focusing on etiology, diagnostic modalities, and therapies. We attempt to discuss relevance from the preterm and the term perspective. Emerging evidence implicating chorioamnionitis as a significant contributor to neonatal brain injury is discussed. Therapeutic modalities such as magnetic resonance imaging and electrophysiological monitoring offer some potentially new tools for the clinician. An exploding series of basic advances suggest several potentially new strands of therapy. We discuss two that deserve further clinical exploration, namely anti-inflammatory strategies and thread hormone supplementation. In the arena of therapy, however, the paucity of large trials from which to guide therapies is a predominant theme, leaving a large reservoir of uncertainty for the clinician.

Anti-Inflammatory Agents↗

A randomized trial of 72- versus 24-hour intravenous tubing set changes in newborns receiving lipid therapy.

OBJECTIVE: To compare the microbial contamination rate of infusate in the intravenous tubing of newborns receiving lipid therapy, replacing the intravenous delivery system at 72-hour versus 24-hour intervals. DESIGN: Infants requiring intravenous lipid therapy were randomly assigned to have intravenous sets changed on a 72- or a 24-hour schedule, in a 3:1 ratio, in order to compare the infusate contamination rates in an equivalent number of tubing sets. SETTING: A 35-bed, teaching, referral, neonatal intensive-care unit (NICU). PARTICIPANTS: All neonates admitted to the NICU for whom intravenous lipid was ordered. METHODS: Patients were randomized in pharmacy, on receipt of the order for intravenous lipid therapy, to either 72- or 24-hour administration set changes, and followed until 1 week after discontinuation of lipids or discharge from the NICU. Microbial contamination of the infusate was assessed in both groups at the time of administration set changes. Contamination rates were analyzed separately for the lipid and amino acid-glucose tubing sets. Patient charts were reviewed for clinical and epidemiological data, including birth weight, gestational age, gender, age at start of lipid therapy, duration of parenteral nutrition, and type of intravenous access. RESULTS: During the study period, 1,101 and 1,112 sets were sampled in the 72- and 24-hour groups, respectively. Microbial contamination rates were higher in the 72-hour group than the 24-hour group for lipid infusions (39/1,101 [3.54%] vs 15/1,112 [1.35%]; P=.001) and for amino acid infusions (12/1,093 [1.10%] vs 4/1,103 [0.36%]; P=.076). Logistic regression analysis controlling for birth weight, gestational age, and type of venous access showed that only the tubing change interval was significantly associated with lipid set contaminations (odds ratio, 2.69; P=.0013). The rate of blood cultures ordered was higher in the 72- versus the 24-hour group (6.11 vs 4.99 per 100 patient days of total parenteral nutrition; P=.017), and a higher proportion of infants randomized to the 72-hour group died (8% vs 4%; P=.05), although the excess deaths could not clearly be attributed to bacteremia. CONCLUSION: Microbial contamination of infusion sets is significantly more frequent with 72- than with 24-hour set changes in neonates receiving lipid solutions. This may be associated with an increased mortality rate.

Bacteremia↗

Estimation of pulmonary deposition of aerosol using gamma scintigraphy.

Following delivery of technetium 99m-labeled aerosols through a ventilator circuit, the amount of radioactivity in the lungs of 58 ventilated rabbits was estimated first by gamma scintigraphy via gamma camera and later by direct counting of the excised lungs (n = 116 specimens) with a gamma counter. The in situ radioactivity measured via scintigraphy was closely correlated with the gamma counter ex vivo tissue counts of the radioactivity (R2 = 0.997, P < 0.001). Overall, gamma scintigraphy gave slightly lower values of activity than the tissue counts from the gamma counter, but the limits of agreement between the two measurements were narrow enough for us to consider that the tissue and scintigraphy methods were in agreement. We conclude that gamma scintigraphy provides a convenient and noninvasive means for the accurate estimation of aerosol deposition in the lungs of small animals and possibly in small infants.

Aerosols↗

Autopsy in a neonatal intensive care unit: utilization patterns and associations of clinicopathologic discordances.

OBJECTIVES: (1) To develop methods to describe autopsy utilization patterns in a neonatal intensive care unit. (2) To identify classes of patients likely to have clinicopathologic concordance or discordance. METHODS: Five hundred forty-five consecutive neonatal intensive care unit deaths (338 autopsied, rate 62%) in a regional tertiary/quaternary care neonatal intensive care unit for referred infants (65,000 annual births) were classified in six clinical diagnostic groups (anomalies, cardiac anomalies, hypoxic ischemic encephalopathy, prematurity and its complications, infections, and other) and rated in three levels of certainty of clinical diagnosis as "gold standard" certainty, almost complete certainty, and less certain than the latter. Clinicopathologic discordances were rated in three classes using clinical, pathologic, and multidisciplinary mortality conference records. The proportions of autopsied cases, cases with major discordances, and cases with no discordances were compared and analyzed in relation to diagnostic group and level of certainty. RESULTS: Performance of autopsy was associated with clinical diagnostic uncertainty (p = 0.008). Major discordances with implications for outcome (Class I) were found in 3%, and without implications for outcome (Class II) in 15% of cases; 42% of cases had no discordances. Major discordance rate varied inversely with the degree of diagnostic certainty (p = 0.000) and varied among clinical groups. CONCLUSIONS: (1) Autopsy was used most for cases with potential for high yields. (2) Clinicopathologic discordances were more frequent and important in certain clinical diagnostic groups (prematurity, other) and with high levels of diagnostic uncertainty. When the diagnostic "gold standard" is available during life, autopsy will provide little information.

Autopsy↗

Nebulisation of surfactants in an animal model of neonatal respiratory distress.

AIMS: To evaluate pulmonary deposition and gas exchange following nebulisation of two surfactants by either a jet or an ultrasonic nebuliser. METHOD: After bronchoalveolar lavage (BAL), 19 rabbits were ventilated in four groups. Group A1 (n = 5) and A2 (n = 6) received Technetium-99m labelled Exosurf, and groups B1 (n = 4) and B2 (n = 4) received radiolabelled Survanta. Groups A1 and B1 received jet nebuliser therapy, whereas groups A2 and B2 received ultrasonic nebuliser. Pulmonary deposition, distribution, and blood gases were determined. RESULTS: Pulmonary deposition as per cent of initial dose and mg lipid) was 0.28(0.10)% or 0.59(0.21) mg in group A1, 1.05(0.23)% or 2.21(0.48) mg in group A2, 0.08(0.02)% or 0.30(0.08) mg in group B1, and 0.09(0.02)% or 0.34(0.08) mg in group B2. Deposition in group A2 was greater than in other groups (p = 0.001). Group A2 showed a small improvement in blood gases. CONCLUSIONS: Even the highest deposition--ultrasonic nebuliser with Exosurf--achieved limited clinical effect. The aerosol route is currently not effective for surfactant treatment.

Aerosols↗

Delivery of metered dose inhaler aerosols to paralyzed and nonparalyzed rabbits.

OBJECTIVE: To assess whether paralysis alters pulmonary deposition of albuterol delivered by metered dose inhaler and spacer to small animals. DESIGN: A parallel group study of intubated and ventilated rabbits. INTERVENTIONS: Animals in group 1 (n = 7) were paralyzed with intravenous pancuronium, and ventilated at a rate of 30 breaths/ min. The animals in group 2 (n = 6) were ventilated at a rate of 10 breaths/min under light anesthesia without paralysis. In this latter group, spontaneous respiration continued at a rate of 40 to 50 breaths/min. Both groups were maintained at PaCO2 of 35 to 40 torr (4.7 to 5.3 kPa), and other ventilatory settings were identical. MEASUREMENTS AND MAIN RESULTS: Technetium-99m labeled albuterol aerosol was delivered by metered dose inhaler via a spacer device to both groups. Pulmonary deposition of the aerosol, determined by measuring the radioactivity in the lung tissues at autopsy, was expressed as percent of the total radioactivity dispensed by the metered dose inhaler. Group 2 showed significantly greater lung deposition than group 1 (0.510 +/- 0.076 [SEM]% vs. 0.226 +/- 0.054%, p = .0094). Deposition in the airway, the endotracheal tube, and the ventilator circuit did not differ significantly. CONCLUSION: Metered dose inhaler delivery of aerosolized medications to ventilated rabbits is significantly enhanced if respiration is not controlled. This observation might have implications for the delivery of therapeutic aerosols to newborns and young infants receiving slow, intermittent, mandatory ventilation.

Aerosols↗

[18F]fluorodeoxyglucose uptake in neonatal acute lung injury measured by positron emission tomography.

The objective of this study was to evaluate positron emission tomography (PET) of [18F]fluorodexoyglucose (18FDG) uptake as a measure of neonatal acute lung injury. Inasmuch as intrapulmonary sequestration of neutrophils is a hallmark of acute lung injury, quantification of neutrophil activity using 18FDG may offer a novel, in vivo technique to examine the progression and resolution of this disease. Ten newborn piglets were studied: six received bronchoalveolar lavage followed by 4 h of high pressure ventilation of create acute lung injury. Four healthy piglets served as controls. 18FDG (0.8 mCi/kg; 29.6 MBq) was given i.v. and PET (ECAT 953/31, Siemens) was performed for 90 min. During PET, all animals were sedated, paralyzed, and ventilated to maintain normal blood gases. The time course of radioactivity in lung regions and in plasma was used to calculate the rate constant for the metabolic trapping of 18FDG in tissue according to the method of C. S. Patlak. Median 18FDG influx constants were significantly higher in injured piglets (0.0187 min-1) than in control piglets (0.0052 min-1) (p < 0.01). Moreover, consistent with the 18FDG uptake data, injured piglets had moderate to severe injury on lung histology whereas control piglets had only slight and focal histologic changes. We conclude that PET of 18FDG uptake is an accurate, readily repeatable in vivo measure of neonatal acute lung injury.

Animals↗

Pulmonary deposition of salbutamol aerosol delivered by metered dose inhaler, jet nebulizer, and ultrasonic nebulizer in mechanically ventilated rabbits.

The deposition efficiency of three methods of aerosol delivery of salbutamol into lungs of ventilated rabbits was compared: 1) metered dose inhaler (MDI) with holding chamber (HC), 2) jet nebulizer (JN), and 3) ultrasonic (US) nebulizer. The latter system was tested using two different sized medication reservoirs, a large (20 mL) cup (US20) and a small (10 mL) cup (US10). After delivery of technetium-99m-labeled salbutamol aerosol, deposition in the lungs, trachea, and ventilator circuit were estimated by a gamma counter. Total pulmonary deposition [mean(SEM)] as a percentage of the prescribed drug was: MDI + HC 0.22(0.05)%; JN 0.48(0.05)%; US20 0.90(0.13)%; US10 3.05(0.49)%. Only the deposition from the US10 was statistically significantly higher than the other modes (p < 0.05). Dynamic scintigraphy showed that, among the nebulizers, the US10 continued to deliver medication for longer than either the JN or the US20. We conclude that the US10 appears to be more efficient in delivering aerosol to the lung in this rabbit model and merits further evaluation for clinical efficiency.

Administration, Inhalation↗

Efficiency of aerosol medication delivery from a metered dose inhaler versus jet nebulizer in infants with bronchopulmonary dysplasia.

The best means for optimal delivery of drugs into lungs of infants with bronchopulmonary dysplasia (BPD) is uncertain. We aimed to measure radio-aerosol deposition of salbutamol by jet nebulizer and metered dose inhalers (MDI) in ventilated and non-ventilated BPD infants. In a randomized, crossover sequence, salbutamol lung deposition was measured using an MDI (2 puffs or 200 micrograms) or sidestream jet nebulizer (5 minutes of nebulization with 100 micrograms/kg) in 10 ventilated (mean birthweight, 1,101 g) and 13 non-ventilated (mean birthweight, 1,093 g) prematurely born infants. Non-ventilated infants inhaled aerosol through a face mask, connected to a nebulizer or an MDI and spacer (Aerochamber). Ventilated infants received aerosol from an MDI + MV15 Aerochamber or a nebulizer inserted in the ventilator circuit. Lung deposition by both methods was low: mean (SEM) from the MDI was 0.67 (0.17)% of the actuated dose, and from the nebulizer it was 1.74 (0.21)% and 0.28 (0.04)% of the nebulized and initial reservoir doses, respectively. Corresponding figures for the ventilated infants were 0.98 (0.19)% from the MDI and 0.95 (0.23)% and 0.22 (0.08)% from the nebulizer. In both groups, and for both methods of delivery, there was marked inter-subject variability in lung deposition and a tendency for the aerosol to be distributed to the central lung regions.

Aerosols↗

A new measure of parent satisfaction with medical care provided in the neonatal intensive care unit.

The objective of this study was to develop a valid and reliable discriminative index that measures parent satisfaction with the medical care of their infant in the NICU. We developed an initial questionnaire (Item Reduction Questionnaire) by reviewing the literature, surveying 63 NICU clinicians, and interviewing 125 parents of infants in 2 tertiary level NICUs regarding what they liked and disliked about the medical care of their infants. We administered the Item Reduction Questionnaire, which included 154 items, to 60 parents, who rated the frequency and importance of these items. We included the items identified most frequently as sources of dissatisfaction and rated most important in a second, briefer instrument, the Neonatal Index of Parent Satisfaction (NIPS). To measure reliability we administered the NIPS to 47 parents twice, separated by a 1-week interval. We assessed validity by comparing actual to predicted correlations between NIPS scores and other measures: parent's global rating of satisfaction, medical caregiver ratings of mother's satisfaction, medical caregiver ratings of father's satisfaction, and parents' perception of their infant's health status. We also compared mean NIPS scores for parents who did and who did not report incidents when errors occurred in the medical care of the infant. Of 154 items generated, we included 27 in the NIPS. The intraclass correlation between two administrations of the NIPS to the same 47 parents was 0.71. As predicted, there was a high correlation (0.61) between the NIPS score and parent global rating of satisfaction, and much lower correlations with other variables. Mean NIPS scores for parents who did and who did not report errors differed significantly (difference, 14.6; 95% CI around difference, 5.8-23.5; p < 0.001). The NIPS is likely to be a useful measure for discriminating between parents who differ in terms of their satisfaction with the medical care of their infant in the NICU.

Adult↗

Chest position and pulmonary deposition of surfactant in surfactant depleted rabbits.

AIMS: To investigate the correlation between chest position and the distribution of surfactant in the lungs of surfactant depleted rabbits, to corroborate current guidelines on the intratracheal instillation of exogenous surfactant in newborns. METHODS: Twelve tracheotomised rabbits, depleted of pulmonary surfactant by saline bronchoalveolar lavage, were given intratracheal 99m Technetium labelled Exosurf in three positions (prone, right side down, and left side down) (n = 4 in each group). They were monitored for 10 minutes using dynamic gamma scintigraphy monitoring. Instillation completed, the lateral lying animals were turned to the opposite side to determine whether redistribution of the surfactant had taken place. The amount of radiolabelled surfactant deposited at the peripheral, central, dorsal and ventral parts of the lungs was then estimated by gamma counting of the lung sections at necropsy. RESULTS: Both gamma scintigraphy and gamma counting showed similar rates and total amount of surfactant accumulation in both lungs of the prone animals. In the lateral lying animals surfactant accumulated at a significantly faster rate in the dependent lungs: the amount of surfactant deposition was three to 14-fold that in the raised lungs (p = 0.017; nested ANOVA). Changing the chest position immediately after instillation did not redistribute the surfactant. In all three groups of animals there was no significant difference in deposition between the peripheral, central, ventral and dorsal parts of the lungs. CONCLUSIONS: Pulmonary distribution of intratracheally instilled surfactant is largely determined by gravity, and changing the chest position after instillation does not result in any redistribution of the surfactant. During the instillation of exogenous surfactant to newborn infants, keeping the chest in the horizontal position may therefore result in the most even distribution of the surfactant in the two lungs. Further deposition studies are required to evaluate the validity of the current recommendations on surfactant administration.

Animals↗

Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-alpha, macrophage inflammatory protein-2, interleukin-1 beta, and interleukin-6 but not RANTES or transforming growth factor-beta 1 mRNA expression in acute lung inflammation.

Using a rat model of acute lung inflammation induced by intratracheal instillation of lipopolysaccharide (LPS), we investigated the kinetics of mRNA expression and the potential cellular sources of tumor necrosis factor-alpha (TNF-alpha), macrophage inflammatory protein-2 (MIP-2), interleukin (IL)-1 beta, IL-6, RANTES, and transforming growth factor-beta 1 (TGF-beta 1). By Northern blot analysis, TNF-alpha and MIP-2 mRNAs in total lung tissue increased markedly by 30 min and peaked by 1 h after LPS exposure, whereas expression of IL-1 beta and IL-6 was not detected until 1 h and peaked within 6 h. In contrast, neither RANTES nor TGF-beta 1 mRNA was induced by LPS throughout 72 h, although a basal expression was detected in both saline- and LPS-treated lung tissues. At 1 h after LPS, the bronchoalveolar lavage (BAL) fluid contained about 98% alveolar macrophages (AM), whereas by 6 or 12 h, 88% of BAL cells were polymorphonuclear neutrophils (PMN). Upon extraction of total RNA after separation of AM from PMN in BAL, Northern analysis showed that at 1 h, AM expressed pronounced signals for TNF-alpha, MIP-2, IL-1 beta, and IL-6. At 6 and 12 h, however, while cytokine transcripts decreased in AM, PMN exhibited strong signals for these cytokines. A low basal noninducible signal for TGF-beta 1 but not RANTES was detected in both AM and PMN. Finally, by in situ hybridization techniques, PMN in the lung tissue, particularly those located in the vicinity of the bronchiole and vasculature, were demonstrated to localize MIP-2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Measurement of functional residual capacity by sulfur hexafluoride in small-volume lungs during spontaneous breathing and mechanical ventilation.

We modified a sulfur hexafluoride (SF6) washout technique to allow functional residual capacity (FRC) determinations in small-volume lungs both during spontaneous breathing and controlled mechanical ventilation. This method facilitates measurements in subjects who attempt spontaneous breaths between ventilator-generated breaths. We wished to confirm the accuracy and precision of the measurements and the method's sensitivity to change. The method uses a pneumotach together with a fast, mainstream infrared SF6 sensor mounted between the endotracheal tube and the ventilator circuit. A low flow of pure SF6 is delivered into the constant gas flow of the ventilator circuit to wash in tracer gas at a concentration of less than 2%. The flow signal and the instantaneous SF6 concentration is processed on-line by a computer. The calibration of the SF6 sensor's nonlinear signal and the ability of the flow sensor to reflect flow values precisely near zero flow had a major impact on the accuracy of the FRC estimate. This accuracy was tested by comparing measured FRC values with a dummy lung's true FRC that was varied from 7 to 70 mL. The comparison differed by 0.7 +/- 3.2% (mean +/- SD; range, -5.1 to 7.8%). As a measure of reproducibility (precision) across 20 FRC determinations in five adult rabbits, the average coefficient of variation was 1.7% (range, 0.57 to 4.33%) during continuous positive airway pressure and 1.98% (range, 0.35 to 3.81%) during controlled mechanical ventilation. The method proved sensitive to changes in FRC related to changes in airway pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Resistive and elastic unloading to assist spontaneous breathing does not change functional residual capacity.

Resistive and/or elastic unloading (a negative ventilator impedance, otherwise termed proportional assist ventilation) may be a useful means to assist spontaneous breathing. This only applies if the ventilator accurately provides pressure changes at the airway opening (P(ao)) proportional to the instantaneous flow and/or volume signal of spontaneous breathing and no significant phase lag. We designed such an infant ventilator, which controls the P(ao) by a negative feedback loop, and superimposes a second positive feedback circuit to generate unloading. To test this mode and the ventilator's accuracy in performing the synchronized pressure changes, we examined the functional residual capacity (FRC). We hypothesized that unloading by itself would not alter FRC because P(ao) should return to a preset baseline at end-expiration, and furthermore, that FRC could be actively altered by changing the baseline. Five anesthetized, tracheotomized, spontaneously breathing rabbits [respiratory system compliance 22.4 +/- 4.6 mL/kPa (mean +/- SEM)] were exposed to end-expiratory P(ao) levels of 0, 0.2, 0.4, and 0.6 kPa. At each of these levels a period of regular continuous positive airway pressure (CPAP) was alternated with a period of unloading (-40 mL/kPa ventilator compliance combined with -3 kPa/L/s ventilator resistance). FRC measured by a sulfur hexafluoride washout technique was virtually identical on CPAP and during unloading at equal end-expiratory P(ao) (difference, 1.41% +/- 0.95%), but FRC increased upon elevation of the end-expiratory P(ao) by 29.4 +/- 3.6 mL/kPa on CPAP and 30.2 +/- 3.2 at unloading (difference NS). We conclude that FRC is not destabilized by unloading, but that during unloading, as during CPAP, it depends on the end-expiratory P(ao).

Animals↗