Richard Sindelar

Skin conductance measurements as pain assessment in newborn infants born at 22-27 weeks gestational age at different postnatal age

BACKGROUND To assess pain or stress in newborn infants submitted to intensive care is important but difficult, as different observational pain scales are not always reliable in premature infants. As an indicator of pain, skin conductance (SC) measurements have detected increased sweating in newborn infants >28 gestational age (GA) submitted to heel lancing. OBJECTIVE To measure SC during heel lancing and routine care in newborn infants, born at 22 to 27 GA, with special relation to postnatal age (PNA). METHODS In six infants <28+0 GA and 4 infants ≥28+0 GA spontaneous SC activity and behavioural state (Neonatal Pain Agitation and Sedation Scale (N-PASS)) was measured before, during and after each intervention. Measurements were repeated in each patient at different PNA. RESULTS Baseline SC prior to intervention took longer time to stabilise and was higher in <28 than in ≥28+0 PNA. The combination of heel lancing and squeezing gave an increased SC in <28 PNA, whereas heel lancing alone gave the same SC response in ≥28+0 PNA. A possibly continued immature response in SC measurements was not observed. Oral glucose admission prior to heel lancing increased SC. Routine care did not give any changes in SC. Except during orogastric tube placement no signs of discomfort or pain could be detected by the neonatal pain, agitation and sedation scale (N-PASS) in <28 PNA. CONCLUSION Changes in SC could be detected in infants at <28+0 PNA and related to the combination of heel lancing and squeezing. A maturational development of the SC was observed in infants born <28 GA. SC seems to be able to differentiate between pain and discomfort.

Effects of the inspiratory pressure waveform during patient-triggered ventilation on pulmonary stretch receptor and phrenic nerve activity in cats.

Objective To examine the effects of square wave, sinusoidal, and linear inspiratory pressure waveforms during pressure-controlled assist/control ventilation on the firing pattern of pulmonary stretch receptors and phrenic nerve activity. Design Experimental, comparative study. Setting Research laboratory at a university biomedical center. Subjects Nine anesthetized, endotracheally intubated young cats (2.5–3.4 kg). Intervention With interposed periods of continuous positive airway pressure (0.2 kPa), each cat was exposed to periods of assist/control ventilation with three different pressure waveforms, where the peak inspiratory pressure (0.74 ± 0.13 kPa), end-expiratory pressure (0.2 ± 0.02 kPa), and tidal volume (14.9 ± 5.22 mL/kg) were kept constant. Preset controlled ventilator rate was set below the rate of spontaneous breathing, and the mechanical inflation time equaled the inspiratory time during spontaneous breathing on continuous positive airway pressure. Measurements and Main Results Respiratory rate and arterial blood gases did not change between the three pressure waveforms during assist/control ventilation. Peak pulmonary stretch receptor activity was lower and mean phrenic nerve activity higher during continuous positive airway pressure than during assist/control ventilation (p < .05). Peak inspiratory pulmonary stretch receptor activity was the same with all three pressure waveforms (82 ± 17 impulses·sec−1) but occurred earlier with square wave than with sinusoidal or linear pressure waveforms (p < .05). The total number of impulses in the phrenic nerve activity burst was smaller with square wave than with the other two pressure waveforms (0.21 ± 0.17 vs. 0.33 ± 0.27 and 0.42 ± 0.30 arbitrary units;p < .05), and the phrenic nerve activity burst duration was shorter with square wave (1.10 ± 0.45 vs. 1.54 ± 0.36 and 1.64 ± 0.25 secs;p < .05). Conclusion Square wave pressure waveform during pressure-controlled assist/control ventilation strongly inhibits spontaneous inspiratory activity in cats. One mechanism for this inhibition is earlier and sustained peak pulmonary stretch receptor activity during inspiration. These findings show that differences in inspiratory pressure waveforms influence the spontaneous breathing effort during assist/control ventilation in cats.

Inhibition of breathing after Surfactant Depletion is Achieved at a Higher Arterial PCO2 during Ventilation with Liquid than with Gas

BackgroundInhibition of phrenic nerve activity (PNA) can be achieved when alveolar ventilation is adequate and when stretching of lung tissue stimulates mechanoreceptors to inhibit inspiratory activity. During mechanical ventilation under different lung conditions, inhibition of PNA can provide a physiological setting at which ventilatory parameters can be compared and related to arterial blood gases and pH.ObjectiveTo study lung mechanics and gas exchange at inhibition of PNA during controlled gas ventilation (GV) and during partial liquid ventilation (PLV) before and after lung lavage.MethodsNine anaesthetised, mechanically ventilated young cats (age 3.8 ± 0.5 months, weight 2.3 ± 0.1 kg) (mean ± SD) were studied with stepwise increases in peak inspiratory pressure (PIP) until total inhibition of PNA was attained before lavage (with GV) and after lavage (GV and PLV). Tidal volume (Vt), PIP, oesophageal pressure and arterial blood gases were measured at inhibition of PNA. One way repeated measures analysis of variance and Student Newman Keuls-tests were used for statistical analysis.ResultsDuring GV, inhibition of PNA occurred at lower PIP, transpulmonary pressure (Ptp) and Vt before than after lung lavage. After lavage, inhibition of inspiratory activity was achieved at the same PIP, Ptp and Vt during GV and PLV, but occurred at a higher PaCO2 during PLV. After lavage compliance at inhibition was almost the same during GV and PLV and resistance was lower during GV than during PLV.ConclusionInhibition of inspiratory activity occurs at a higher PaCO2 during PLV than during GV in cats with surfactant-depleted lungs. This could indicate that PLV induces better recruitment of mechanoreceptors than GV.

A High Ductal Flow Velocity is Associated with Successful Pharmacological Closure of Patent Ductus Arteriosus in Infants 22-27 Weeks Gestational Age

Objective. To identify factors affecting closure of patent ductus arteriosus (PDA) in newborn infants born at 22–27 weeks gestational age (GA) during pharmacological treatment with cyclooxygenase inhibitors. Method. Infants born at 22–27 weeks of GA between January 2006 and December 2009 who had been treated pharmacologically for PDA were identified retrospectively. Medical records were assessed for clinical, ventilatory, and outcome parameters. Echocardiographic examinations during treatment were reviewed. Results. Fifty-six infants were included in the study. Overall success rate of ductal closure with pharmacological treatment was 52%. Infants whose PDA was successfully closed had a higher GA (25 + 4 weeks versus 24 + 3 weeks; P = 0.047), and a higher pretreatment left to right maximal ductal flow velocity (1.6 m/s versus 1.1 m/s; P = 0.023). Correcting for GA, preeclampsia, antenatal steroids, and age at start of treatment, a higher maximal ductal flow velocity was still associated with successful ductal closure (OR 3.04; P = 0.049). Conclusion. Maximal ductal flow velocity was independently associated with success of PDA treatment.

Pulmonary stretch receptor activity during Partial Liquid Ventilation in Cats with Healthy Lungs.

Aim: To study whether pulmonary stretch receptor (PSR) activity in mechanically ventilated young cats with healthy lungs during partial liquid ventilation (PLV) is different from that during gas ventilation (GV). Methods: In 10 young cats (4.4 ± 0.4 months, 2.3 ± 0.3 kg; mean ± SD), PSR instantaneous impulse frequency (PSR fimp) was recorded from single fibres in the vagal nerve during GV and PLV with perfluorocarbon (30 ml/kg) at increasing positive inspiratory pressures (PIP; 1.2, 1.8, 2.2 and 2.7 kPa), and at a positive end-expiratory pressure of 0.5 kPa. Results: All PSRs studied during GV maintained their phasic character with increased impulse frequency during inspiration during PLV. Peak PSRfimp was lower at PIP 1.2 kPa (p < 0.05) and at PIP 2.7 kPa (p = 0.10) during PLV than during GV, giving a lower number of PSR impulses at these two settings during PLV (p < 0.05). Conclusion: The phasic character of PSR activity is similar during GV and PLV. PSR activity is not higher during PLV than during GV in cats with healthy lungs, indicating no extensive stretching of the lung during PLV.

Differential neutrophil chemotactic response towards IL-8 and bacterial N-formyl peptides in term newborn infants

Abstract Background: A prerequisite for an effective innate immunity is the migrative ability of neutrophils to respond to inflammatory and infectious agents such as the intermediate interleukin (IL)-8 and the end-target formyl-methionyl-leucyl-phenylalanine (fMLP) chemoattractants. The aim was to study the chemotactic capacity of neutrophils from newborn infants and adults in response to IL-8 and the bacterial peptide fMLP. Methods: In the under-agarose cell migration assay, isolated leukocytes from healthy adults and from cord blood of healthy term newborn infants were studied with dose responses towards IL-8 and fMLP. The same number of leukocytes (1 × 105 cells), with the same distribution of neutrophils and monocytes, were analyzed in neonates and adults. Chemotaxis was distinguished from randomly migrating neutrophils, and the neutrophil pattern of migration, i.e. the migration distance and the number of migrating neutrophils per distance, was evaluated. Results: In comparison to adults, fewer neutrophils from newborn infants migrated towards IL-8 and for a shorter distance (P < .01, respectively). The number of neutrophils migrating to different gradients of fMLP, the distance they migrated, and the correlation between the number and the distance were the same for neonates and adults. Random migration did not differ in any instance. Conclusion: Chemotaxis of neutrophils from newborn infants was as co-ordinated as neutrophils from adults in response to fMLP, whereas the response to IL-8 was reduced. The differential response of neutrophils from neonates to intermediate and end-target chemoattractants could indicate a reduced infectious response.

Neutrophil Receptor Response to Bacterial N-formyl Peptides is Similar in Term Newborn Infants and Adults in Contrast to IL-8.

We have previously observed that neutrophils from neonates exhibit different migratory responses to intermediate and end‐target chemoattractants compared to adults. The aim of this study was to investigate the effect of the chemoattractants IL‐8 (intermediate) and formyl‐methionyl‐leucyl‐phenylalanine (fMLP; end‐target) on cell surface receptor expression involved in adhesion, migration and granule release of neutrophils from term newborn infants and adults. Heparinized cord blood from 16 healthy term newborn infants delivered by caesarean section and peripheral blood from 17 healthy adults were incubated with 1 μm IL‐8 or 0.1 μm fMLP, previously defined as optimal inducers of neutrophil migration. The leukocytes were labelled with antibodies to cell surface receptors (CD11b, CD15S, CD18, CD35, CD44, CD64, CD65, CD88, CD162, CD181 and CD182). Receptor expression was quantified by flow cytometry analysis. Upregulation of CD11b and downregulation of CD88 and CD182 after stimulation with IL‐8 were more pronounced in adults than in neonates (P < 0.05, P < 0.05 and P ≤ 0.001, respectively), whereas fMLP induced changes in receptor expression that were of the same magnitude in neutrophils from neonates as from adults. We observed similar expression of receptors that mediate adhesion, migration, granule activation and phagocytosis induced by fMLP in neutrophils from neonates and adults. In contrast, differences between neonates and adults, induced by IL‐8, suggest that the neutrophil response to intermediate chemoattractants might lead to a compromised infectious response in newborn infants.

Bacterial N-formyl Peptides Reduce PMA- and Escherichia coli -Induced Neutrophil Respiratory Burst in Term Neonates and Adults

Neutrophil migration and respiratory burst are the prerequisite for efficient first line defense against invading microorganisms. However, migration and respiratory burst can be compromised in adults and especially in newborn infants, where sustained neutrophil accumulation, uncontrolled burst and reduced scavenging of ROS might cause inadvertent tissue damage due to uncontrolled inflammation. The aim of this study was to investigate the modulatory effect of the chemoattractants formyl‐methionyl‐leucyl‐phenylalanine (fMLP) and IL‐8 on respiratory burst in neutrophils from term newborn infants and adults. Whole blood from the umbilical cord of 17 healthy term newborn infants delivered by caesarean section and from 17 healthy adults as reference was preincubated with fMLP or IL‐8 and stimulated with PMA or Escherichia coli bacteria. Respiratory burst was quantified by flow cytometry analysis of dihydrorhodamine 123 fluorescence. fMLP reduced the PMA‐induced respiratory burst of neutrophils from newborn infants and adults by 12% and 21%, respectively (P < 0.05). E. coli‐induced burst was also reduced by fMLP in neutrophils from newborn infants (10%; P < 0.01) and adults (6%; P < 0.05). No such changes were observed with IL‐8. Similar respiratory burst in response to single stimulus with PMA or E. coli was observed in both newborn infants and adults. fMLP reduced PMA‐ and E. coli‐induced respiratory burst of neutrophils in whole blood from term newborn infants as well as in adults. The reduced respiratory burst by fMLP might be a mechanism to reduce the detrimental effects of uncontrolled inflammation during neutrophil migration.

Response of Slowly Adapting Pulmonary Stretch Receptors in Surfactant Depleted Cat Lungs: Before and After Surfactant Replacement 226

Objective: To investigate the response of slowly adapting pulmonary stretch receptors (SAPSRs) to changes in lung volume and airway pressure (Paw).

Oscillatory respiratory mechanics on the first day of life improves prediction of respiratory outcomes in extremely preterm newborns

BackgroundWe aimed to evaluate if lung mechanics measured by forced oscillatory technique (FOT) during the first day of life help identify extremely low gestational age newborns (ELGANs) at risk of prolonged mechanical ventilation (MV) and oxygen dependency.MethodsPositive end-expiratory pressure (PEEP) was increased 2 cmH2O above the clinically set PEEP, then decreased by four 5-min steps of 1 cmH2O, and restored at the clinical value. At each PEEP, FOT measurements were performed bedside during MV. Changes in respiratory mechanics with PEEP, clinical parameters, and chest radiographs were evaluated.ResultsTwenty-two newborns (24+4 ± 1+4 wks gestational age (GA); birth weight 653 ± 166 g) on assist/control ventilation were studied. Infants were ventilated for 40 ± 36 d (range 1–155 d), 11 developed severe bronchopulmonary dysplasia (BPD) and one died before 28 d. Early lung mechanics correlated with days on MV, days of respiratory support, and BPD grade. Effects of increasing PEEP on oscillatory reactance assessed by FOT together with GA and radiographic score predicted days on MV (multilinear model, r2 = 0.73). A logistic model considering the same FOT parameter together with GA predicts BPD development.ConclusionsFOT can be applied bedside in ELGANs, where early changes in lung mechanics with PEEP improve clinical prediction of respiratory outcomes.