Respiratory function monitoring during early resuscitation and prediction of outcomes in prematurely born infants.

OBJECTIVES: Over the last decade, there has been increased use of end-tidal carbon dioxide (ETCO2) and oxygen saturation (SpO2) monitoring during resuscitation of prematurely born infants in the delivery suite. Our objectives were to test the hypotheses that low end-tidal carbon dioxide (ETCO2) levels, low oxygen saturations (SpO2) and high expiratory tidal volumes (VTE) during the early stages of resuscitation would be associated with adverse outcomes in preterm infants. METHODS: Respiratory recordings made in the first 10 min of resuscitation in the delivery suite of 60 infants, median GA 27 (interquartile range 25-29) weeks were analysed. The results were compared of infants who did or did not die or did or did not develop intracerebral haemorrhage (ICH) or bronchopulmonary dysplasia (BPD). RESULTS: Twenty-five infants (42%) developed an ICH and 23 (47%) BPD; 11 (18%) died. ETCO2 at approximately 5 min after birth was lower in infants who developed an ICH, this remained significant after adjusting for gestational age, coagulopathy and chorioamnionitis (p=0.03). ETCO2 levels were lower in infants who developed ICH or died compared to those that survived without ICH, which remained significant after adjustment for gestational age, Apgar score at 10 min, chorioamnionitis and coagulopathy (p=0.004). SpO2 at approximately 5 min was lower in the infants who died compared to those who survived which remained significant after adjusting for the 5-min Apgar score and chorioamnionitis (p=0.021). CONCLUSIONS: ETCO2 and SpO2 levels during early resuscitation in the delivery suite were associated with adverse outcomes.

COVID-associated rhinocerebral mucormycosis: a retrospective analysis of presentation and outcomes.

OBJECTIVES: To comprehensively analyse the disease presentation and mortality of COVID-associated rhino-orbito-cerebral mucormycosis. METHODS: A retrospective analysis of the demographics, clinical and radiographic findings was performed. A binary logistic regression analysis was performed to examine the survival of patients with mucormycosis from hypothesised predictors. RESULTS: A total of 202 patients were included in this study. Statistical significance was demonstrated in the predilection to the male gender, recent history of SARS-COV-2, history of use of corticosteroid and hyperglycemia in this cohort of CAM. The mortality rate was 18.31%. Advanced age, raised HbA1c and intra-orbital extension were found to be predictors adversely affecting survival. CONCLUSION: Early diagnosis, aggressive surgical therapy, early and appropriate medical therapy can help improve outcomes. LEVEL OF EVIDENCE: Level 4.

End-tidal carbon dioxide levels during resuscitation and carbon dioxide levels in the immediate neonatal period and intraventricular haemorrhage.

Abnormal levels of end-tidal carbon dioxide (EtCO2) during resuscitation in the delivery suite are associated with intraventricular haemorrhage (IVH) development. Our aim was to determine whether carbon dioxide (CO2) levels in the first 3 days after birth reflected abnormal EtCO2 levels in the delivery suite, and hence, a prolonged rather than an early insult resulted in IVH. In addition, we determined if greater EtCO2level fluctuations during resuscitation occurred in infants who developed IVH. EtCO2 levels during delivery suite resuscitation and CO2 levels on the neonatal unit were evaluated in 58 infants (median gestational age 27.3 weeks). Delta EtCO2 was the difference between the highest and lowest level of EtCO2. Thirteen infants developed a grade 3-4 IVH (severe group). There were no significant differences in CO2 levels between those who did and did not develop an IVH (or severe IVH) on the NICU. The delta EtCO2 during resuscitation differed between infants with any IVH (6.2 (5.4-7.5) kPa) or no IVH (3.8 (2.7-4.3) kPA) (p < 0.001) after adjusting for differences in gestational age. Delta EtCO2 levels gave an area under the ROC curve of 0.940 for prediction of IVH.Conclusion: The results emphasize the importance of monitoring EtCO2 levels in the delivery suite.What is Known:• Abnormal levels of carbon dioxide (CO2) in the first few days after birth and abnormal end-tidal CO2levels (EtCO2) levels during resuscitation are associated in preterm infants with the risk of developing intraventricular haemorrhage (IVH).What is New:• There were no significant differences in NICU CO2levels between those who developed an IVH or no IVH.• There was a poor correlation between delivery suite ETCO2levels and NICU CO2levels.• Large fluctuations in EtCO2during resuscitation in the delivery suite were highly predictive of IVH development in preterm infants.

Tidal volume monitoring during initial resuscitation of extremely prematurely born infants.

Background Airway obstruction can occur during facemask (FM) resuscitation of preterm infants at birth. Intubation bypasses any upper airway obstruction. Thus, it would be expected that the occurrence of low expiratory tidal volumes (VTes) would be less in infants resuscitated via an endotracheal tube (ETT) rather than via an FM. Our aim was to test this hypothesis. Methods Analysis was undertaken of respiratory function monitoring traces made during initial resuscitation in the delivery suite to determine the peak inflating pressure (PIP), positive end expiratory pressure (PEEP), the VTe and maximum exhaled carbon dioxide (ETCO2) levels and the number of inflations with a low VTe (less than 2.2 mL/kg). Results Eighteen infants were resuscitated via an ETT and 11 via an FM, all born at less than 29 weeks of gestation. Similar inflation pressures were used in both groups (17.2 vs. 18.8 cmH2O, P = 0.67). The proportion of infants with a low median VTe (P = 0.6) and the proportion of inflations with a low VTe were similar in the groups (P = 0.10), as was the lung compliance (P = 0.67). Infants with the lowest VTe had the stiffest lungs (P < 0.001). Conclusion Respiratory function monitoring during initial resuscitation can objectively identify infants who may require escalation of inflation pressures.

Detection of exhaled carbon dioxide following intubation during resuscitation at delivery.

OBJECTIVES: End tidal carbon dioxide (ETCO2) monitoring can facilitate identification of successful intubation. The aims of this study were to determine the time to detect ETCO2 following intubation during resuscitation of infants born prematurely and whether it differed according to maturity at birth or the Apgar scores (as a measure of the infant's condition after birth). DESIGN: Analysis of recordings of respiratory function monitoring. SETTING: Two tertiary perinatal centres. PATIENTS: Sixty-four infants, with median gestational age of 27 (range 23-34)weeks. INTERVENTIONS: Respiratory function monitoring during resuscitation in the delivery suite. MAIN OUTCOME MEASURES: The time following intubation for ETCO2 levels to be initially detected and to reach 4 mm Hg and 15 mm Hg. RESULTS: The median time for initial detection of ETCO2 following intubation was 3.7 (range 0-44) s, which was significantly shorter than the median time for ETCO2 to reach 4 mm Hg (5.3 (range 0-727) s) and to reach 15 mm Hg (8.1 (range 0-827) s) (both P<0.001). There were significant correlations between the time for ETCO2 to reach 4 mm Hg (r=-0.44, P>0.001) and 15 mm Hg (r=-0.48, P<0.001) and gestational age but not with the Apgar scores. CONCLUSIONS: The time for ETCO2 to be detected following intubation in the delivery suite is variable emphasising the importance of using clinical indicators to assess correct endotracheal tube position in addition to ETCO2 monitoring. Capnography is likely to detect ETCO2 faster than colorimetric devices.

Extending access to care across the rural US south: Preliminary results from the Alabama eHealth programme.

PURPOSE: Using a mixed-methods formative evaluation, the purpose of this study was to provide a broad overview of the Alabama eHealth programme set-up and initial patient outcomes. The Alabama eHealth programme uses telemedicine to provide medical care to people living with HIV in rural Alabama. It was led by a community-based organisation, Medical Advocacy and Outreach (MAO), and supported by AIDS United and the Corporation for National Community Service's Social Innovation Fund with matching support from non-federal donors. METHODS: We conducted and transcribed in-depth interviews with Alabama eHealth staff and then performed directed content analysis. We also tracked patients' ( n = 240) appointment attendance, CD4 counts, and viral loads. FINDINGS: Staff described the steps taken to establish the programme, associated challenges (e.g., costly, inadequate broadband in rural areas), and technology enabling this programme (electronic medical records, telemedicine equipment). Of all enrolled patients, 76% were retained in care, 88% had antiretroviral therapy and 75% had a suppressed viral load. Among patients without missing data, 96% were retained in care, 97% used antiretroviral therapy and 93% had suppressed viral loads. There were no statistically significant demographic differences between those with and without missing data. CONCLUSIONS: Patients enrolled in a telemedicine programme evaluation successfully moved through the HIV continuum of care.

Relationship of resuscitation, respiratory function monitoring data and outcomes in preterm infants.

Intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD) are major complications of premature birth. We tested the hypotheses that prematurely born infants who developed an IVH or BPD would have high expiratory tidal volumes (VTE) (VTE > 6 ml/kg) and/or low-end tidal carbon dioxide (ETCO2) levels (ETCO2 levels < 4.5 kPa) as recorded by respiratory function monitoring or hyperoxia (oxygen saturation (SaO2) > 95%) during resuscitation in the delivery suite. Seventy infants, median gestational age 27 weeks (range 23-33), were assessed; 31 developed an IVH and 43 developed BPD. Analysis was undertaken of 31,548 inflations. The duration of resuscitation did not differ significantly between the groups. Those who developed an IVH compared to those who did not had a greater number of inflations with a high VTE and a low ETCO2, which remained significant after correcting for differences in gestational age and birth weight between groups (p = 0.019). Differences between infants who did and did not develop BPD were not significant after correcting for differences in gestational age and birth weight. There were no significant differences in the duration of hyperoxia between the groups.Conclusions: Avoidance of high tidal volumes and hypocarbia in the delivery suite might reduce IVH development. What is known • Hypocarbia on the neonatal unit is associated with the development of intraventricular haemorrhage (IVH) and bronchopulmonary dysplasia (BPD). What is new • Infants who developed an IVH compared to those who did not had significantly more inflations with high expiratory tidal volumes and low ETCO2s.

Inflation pressures and times during initial resuscitation in preterm infants.

BACKGROUND: The optimal combination of inflation pressures and times to produce adequate expiratory tidal volumes during initial resuscitation in prematurely born infants has not been determined. The aim of this study was therefore to assess combinations of inflation pressures and times and the resulting expiratory tidal volume levels using a respiratory function monitor. METHODS: Sixty-four infants born before 34 weeks of gestation were studied. The infants were divided according to whether the inflation pressure (peak inflation pressure minus positive end expiratory pressure) was < or ≥20 cmH2 O during the first five inflations delivered by a face mask, and those groups were then subdivided according to whether the inflation time was < or ≥1.5 s. RESULTS: Inflation pressure ≥20 cmH2 O compared with lower pressure at both inflation times produced significantly higher expiratory tidal volume. Longer compared with shorter inflation times when the inflation pressure was ≥20 cmH2 O resulted in no significant difference in expiratory tidal volume. At <20 cmH2 O inflation pressure, longer inflation time overall resulted in higher end tidal volume, but the majority of infants had a tidal volume less than the anatomical dead space. CONCLUSIONS: At higher inflation pressure, a longer inflation time was not necessary to increase expiratory tidal volume.

In vitro assessment of the effect of proportional assist ventilation on the work of breathing.

UNLABELLED: During proportional assist ventilation, elastic and resistive unloading can be delivered to reduce the work of breathing (WOB). Our aim was to determine the effects of different levels of elastic and resistive unloading on the WOB in lung models designed to mimic certain neonatal respiratory disorders. Two dynamic lung models were used, one with a compliance of 0.4 ml/cm H2O to mimic an infant with respiratory distress syndrome and one with a resistance of 300 cm H2O/l/s to mimic an infant with bronchopulmonary dypslasia. Pressure volume curves were constructed at each unloading level. Elastic unloading in the low compliance model was highly effective in reducing the WOB measured in the lung model; the effective compliance increased from 0.4 ml/cm H2O at baseline to 4.1 ml/cm H2O at maximum possible elastic unloading (2.0 cm H2O/ml). Maximum possible resistive unloading (200 cm H2O/l/s) in the high-resistance model only reduced the effective resistance from 300 to 204 cm H2O/l/s. At maximum resistive unloading, oscillations appeared in the airway pressure waveform. CONCLUSION: Our results suggest that elastic unloading will be helpful in respiratory conditions characterised by a low compliance, but resistive unloading as currently delivered is unlikely to be of major clinical benefit. WHAT IS KNOWN: • During PAV, the ventilator can provide elastic and resistive unloading. What is New: • Elastic unloading was highly effective in reducing the work of breathing. • Maximum resistive unloading only partially reduced the effective resistance.

Prediction of infant extubation outcomes using the tension-time index.

OBJECTIVE: The tension-time index of the diaphragm (TTdi) is a composite assessment of the load on and the capacity of the diaphragm. TTmus is a non-invasive tension-time index of the respiratory muscles. Our aim was to determine whether TTdi or TTmus predicted extubation outcome and performed better than respiratory muscle strength (Pimax, Pdimax), respiratory drive (P0.1) and work of breathing (transdiaphragmatic pressure-time product (PTPdi)) or routinely available clinical data. DESIGN: Prospective study. SETTING: Tertiary neonatal intensive care unit. PATIENTS: Sixty infants, median gestation age 35 (range 23-42) weeks and postnatal age of 55 (range 1-115) days. INTERVENTIONS: Airway occlusions were performed to measure Pimax, Pdimax and P0.1. TTdi and PTPdi were derived from measurements of transdiaphragmatic pressure. TTmus was derived from airway pressure measurements. Measurements were made within 6 h of extubation. MAIN OUTCOME MEASURES: Extubation failure defined as reintubation within 48 h of extubation. RESULTS: Twelve infants failed extubation. The infants who failed extubation were significantly more immature (medians 25 vs 37 weeks) and of greater postnatal age (23 vs 5 days) and had higher TTdi (0.15 vs 0.04) and TTmus (0.17 vs 0.08). TTdi and TTmus were only significantly better predictors than the peak inflation pressure immediately prior to extubation and did not perform significantly better than gestational age or birth weight. CONCLUSIONS: Assessment of TTdi and TTmus cannot be recommended for use in routine clinical practice.

Seizure following chemotherapy (paclitaxel and cisplatin) in a patient of carcinoma cervix.

Cisplatin and paclitaxel both can cause peripheral neurotoxicity as an adverse effect; however, central nervous system neurotoxicity in the form of seizures is rare. We report a case of a 36-year-old female patient of metastatic carcinoma cervix, who developed seizure shortly after cisplatin infusion. Her laboratory investigations were within normal limits. Computed tomography scan and magnetic resonance imaging of the brain did not reveal brain primary metastasis or meningeal carcinomatosis. She had no complaints of fever, no signs and symptoms of infection, and no history of seizure nor was she on any medication predisposing to such an event. Excluding several causes, seizure was thought to be most likely related to the chemotherapy and cisplatin was the more likely agent in view of observed temporal relationship with the adverse event.

Volume-targeted versus pressure-limited ventilation in infants born at or near term.

Our aims were to determine whether volume-targeted ventilation (VTV) or pressure-limited ventilation (PLV) reduced the time to successful extubation and if any difference was explained by a lower work of breathing (WOB), better respiratory muscle strength or less thoracoabdominal asynchrony (TAA) and associated with fewer hypocarbic episodes. Infants born at ≥34 weeks of gestational age were randomised to VTV or PLV. The WOB was assessed by the transdiaphragmatic pressure time product, respiratory muscle strength by the maximum inflation (Pimax) and expiratory (Pemax) pressures and TAA assessed using uncalibrated respiratory inductance plethysmography. Forty infants, median gestational age of 39 (range 34-42) weeks, were recruited. The time to successful extubation did not differ between the two groups (median 25, range 2.5-312 h (VTV) versus 33.5, 1.312 h (PLV)) (p = 0.461). There were no significant differences between the groups with regard to the WOB, respiratory muscle strength or the TAA results. The median number of hypocarbic episodes was 1.5 (range 0-8) in the VTV group versus 4 (range 1-13) in the PLV group (p = 0.005). CONCLUSION: In infants born at or near term, VTV compared to PLV did not reduce the time to successful extubation but was associated with significantly fewer hypocarbic episodes. WHAT IS KNOWN: In prematurely born infants, volume-targeted ventilation (VTV) compared to pressure-limited ventilation (PLV) reduces bronchopulmonary dysplasia or death. In addition, VTV is associated in prematurely born infants with lower incidences of pneumothorax, intraventricular haemorrhage and hypocarbic episodes. WHAT IS NEW: Despite a high morbidity, few studies have investigated optimum ventilation strategies for infants born at or near term. In a RCT, we have demonstrated VTV versus PLV in infants ≥34 weeks gestation was associated with significantly fewer hypocarbic episodes.

Proportional assist versus assist control ventilation in premature infants.

During proportional assist ventilation (PAV), the applied pressure is servo-controlled based on continuous input from the infant's breathing. In addition, elastic and resistive unloading can be employed to compensate for the abnormalities in the infant's lung mechanics. The aim of this study was to test the hypothesis that in very prematurely born infants remaining ventilated beyond the first week, PAV compared to assist control ventilation (ACV) would be associated with superior oxygenation. A randomised crossover study was undertaken. Infants were studied for 4 hours each on PAV and ACV in random order; at the end of each 4-h period, the oxygenation index (OI) was calculated. Eight infants, median gestational age of 25 (range 24-33) weeks, were studied at a median of 19 (range 10-105) days. It had been intended to study 18 infants but as all the infants had superior oxygenation on PAV (p = 0.0039), the study was terminated after recruitment of eight infants. The median inspired oxygen concentration (p = 0.049), mean airway pressure (p = 0.012) and OI (p = 0.012) were all lower on PAV. CONCLUSION: These results suggest that PAV compared to ACV is advantageous in improving oxygenation for prematurely born infants with evolving or established BPD. WHAT IS KNOWN: During proportional assist ventilation (PAV), the applied pressure is servo controlled throughout each spontaneous breath. Elastic and resistive unloading can compensate for the infant's abnormalities in lung mechanics. WHAT IS NEW: In a randomised crossover study, infants with evolving/established BPD were studied on PAV and ACV each for 4 h. The oxygenation index was significantly lower on PAV in all infants studied.

Evaluation of respiratory function monitoring at the resuscitation of prematurely born infants.

UNLABELLED: Our aim was to determine whether neonatal trainees found respiratory function monitoring (RFM) helpful during the resuscitation of prematurely born infants, what decisions they made on the basis of RFM and whether those decisions were evidence based. Fifty one trainees completed an electronic questionnaire. Eighty-three percent found the tidal volume display useful, 59 % altered the inflation pressure based on the tidal volume: 52 % considered 5 ml/kg adequate; 33 % 4 ml/kg; 13 % 6 ml/kg; and 2 % 7 ml/kg, despite no evidence on which to decide was the optimum tidal volume. If there was no detectable expired carbon dioxide (CO2), 30 trainees said they would reintubate, yet the absence of expired CO2 can indicate inadequate vasodilation of the pulmonary circulation rather than inappropriate placement of the endotracheal tube. If there was no chest wall expansion, but expired CO2, a third of junior trainees would reintubate which is inappropriate. If the oxygen saturation (SaO2) was <85 % at 1 min, no senior trainee, but 50 % of junior trainees would increase the inspired oxygen. The majority of healthy babies have an SaO2 > 85 % by 1 min. CONCLUSIONS: The usefulness of respiratory function monitoring for trainees during neonatal resuscitation is often not evidence based.

Crossover study of proportional assist versus assist control ventilation.

OBJECTIVE: To test the hypothesis that in very prematurely born infants remaining ventilated beyond the first week, proportional assist ventilation (PAV) compared with assist control ventilation (ACV) would be associated with reduced work of breathing, increased respiratory muscle strength and less ventilator-infant asynchrony which would be associated with improved oxygenation. DESIGN: Randomised crossover study. SETTING: Tertiary neonatal unit. PATIENTS: 12 infants with a median gestational age of 25 (range 24-26) weeks were studied at a median of 43 (range 8-86) days. INTERVENTIONS: Infants were studied for 1 h each on PAV and ACV in random order. MAIN OUTCOME MEASURES: At the end of each hour, the work of breathing (assessed by measuring the diaphragmatic pressure time product), thoracoabdominal asynchrony and respiratory muscle strength (maximal inspiratory pressure, maximal expiratory pressure (Pemax) and maximal transdiaphragmatic pressure (Pdimax)) were assessed. Blood gas analysis was performed and the oxygenation index (OI) calculated. RESULTS: After 1 h on PAV compared with 1 h on ACV, the median OI (5.55 (range 5-11) vs 10.10 (range 7-16), p=0.002) and PTP levels were lower (217 (range 59-556) cm H2O.s/min vs 309 (range 55-544) cm H2O.s/min, p=0.005), while Pdimax (44.26 (range 21-66) cm H2O vs 37.9 (range 19-45) cm H2O, p=0.002) and Pemax (25.6 (range 6.5-42) cm H2O vs 15.9 (range 3-35) cm H2O levels p=0.010) were higher. CONCLUSIONS: These results suggest that PAV compared with ACV may have physiological advantages for prematurely born infants who remain ventilated after the first week after birth.

How to ventilate term babies.

Infants born at term frequently require mechanical ventilation and suffer significant mortality and morbidity. Yet, there have been few randomised trials (RCTs) exclusively of term born infants and when term born infants have been included in studies, a sub-analysis of their results has rarely been undertaken. The limited evidence demonstrates in term born infants that there are no benefits in using rates >60bpm during conventional mechanical ventilation (CMV) or using synchronous intermittent mandatory ventilation. Pressure support ventilation may reduce their work of breathing (WOB). During volume targeted ventilation, a volume targeted (VT) level of 6mls/kg reduces the WOB compared to a lower level or no VT. High frequency oscillatory ventilation in infants born at or near term with severe respiratory failure does not reduce mortality, oxygen dependency at 28 days or intracranial haemorrhage. RCTs with long term outcome are required to determine the optimum ventilatory modes in term born infants.