Effect of mattress deflection on CPR quality assessment for older children and adolescents

Appropriate chest compression (CC) depth is associated with improved CPR outcome. CCs provided in hospital are often conducted on a compliant mattress. The objective was to quantify the effect of mattress compression on the assessment of CPR quality in children. Methods: A force and deflection sensor (FDS) was used during CPR in the Pediatric Intensive Care Unit and Emergency Department of a children's hospital. The sensor was interposed between the chest of the patient and hands of the rescuer and measured CC depth. Following CPR event, each event was reconstructed with a manikin and an identical mattress/backboard/patient configuration. CCs were performed using FDS on the sternum and a reference accelerometer attached to the spine of the manikin, providing a means to Calculate the mattress deflection. Results: Twelve CPR events with 14,487 CC (11 patients, median age 14.9 years) were recorded and reconstructed: 9 on ICU beds (9296 CC), 3 on stretchers (5191 CC). Measured mean CC depth during CPR was 47 +/- 8 mm on ICU beds, and 45 +/- 7 mm on stretcher beds with overestimation of 13 +/- 4 mm and 4 +/- 1 mm, respectively, due to mattress compression. After adjusting for this, the proportion of CC that met the CPR guidelines decreased from 88.4 to 31.8% on ICU beds (p < 0.001), and 86.3 to 64.7% on stretcher (p < 0.001 The proportion of appropriate depth CC was significantly smaller on ICU beds (p < 0.001). Conclusion: CC conducted on a non-rigid surface may not be deep enough. FDS may overestimate CC depth by 28% on ICU beds, and 10% on stretcher beds

Factors Affecting the Course of Resuscitation From Cardiac Arrest With Pulseless Electrical Activity in Children and Adolescents

Background: Although in-hospital pediatric cardiac arrests and cardiopulmonary resuscitation occur >15,000/year in the US, few studies have assessed which factors affect the course of resuscitation in these patients. We investigated transitions from Pulseless Electrical Activity (PEA) to Ventricular Fibrillation/pulseless Ventricular Tachycardia (VF/pVT), Return of Spontaneous Circulation (ROSC) and recurrences from ROSC to PEA in children and adolescents with in-hospital cardiac arrest. Methods: Episodes of cardiac arrest at the Children's Hospital of Philadelphia were prospectively registered. Defibrillators that recorded chest compression depth/rate and ventilation rate were applied. CPR variables, patient characteristics and etiology, and dynamic factors (e.g. the proportion of time spent in PEA or ROSC) were entered as time-varying covariates for the transition intensities under study. Results: In 67 episodes of CPR in 59 patients (median age 15 years) with cardiac arrest, there were 52 transitions from PEA to ROSC, 22 transitions from PEA to VF/pVT, and 23 recurrences of PEA from ROSC. Except for a nearly significant effect of mean compression depth beyond a threshold of 5.7 cm, only dynamic factors that evolved during CPR favored a transition from PEA to ROSC. The latter included a lower proportion of PEA over the last 5 min and a higher proportion of ROSC over the last 5 min. Factors associated with PEA to VF/pVT development were age, weight, the proportion spent in VF/pVT or PEA the last 5 min, and the general transition intensity, while PEA recurrence from ROSC only depended on the general transition intensity. Conclusion: The clinical course during pediatric cardiac arrest was mainly influenced by dynamic factors associated with time in PEA and ROSC. Transitions from PEA to ROSC seemed to be favored by deeper compressions.publishedVersio

Training Hospital Providers in Basic CPR Skills in Botswana: Acquisition, Retention and Impact of Novel Training Techniques

Objective Globally, one third of deaths each year are from cardiovascular diseases, yet no strong evidence supports any specific method of CPR instruction in a resource-limited setting. We hypothesized that both existing and novel CPR training programs significantly impact skills of hospital-based healthcare providers (HCP) in Botswana. Methods HCP were prospectively randomized to 3 training groups: instructor led, limited instructor with manikin feedback, or self-directed learning. Data was collected prior to training, immediately after and at 3 and 6 months. Excellent CPR was prospectively defined as having at least 4 of 5 characteristics: depth, rate, release, no flow fraction, and no excessive ventilation. GEE was performed to account for within subject correlation. Results Of 214 HCP trained, 40% resuscitate ≥1/month, 28% had previous formal CPR training, and 65% required additional skills remediation to pass using AHA criteria. Excellent CPR skill acquisition was significant (infant: 32% vs. 71%, p \u3c 0.01; adult 28% vs. 48%, p \u3c 0.01). Infant CPR skill retention was significant at 3 (39% vs. 70%, p \u3c 0.01) and 6 months (38% vs. 67%, p \u3c 0.01), and adult CPR skills were retained to 3 months (34% vs. 51%, p = 0.02). On multivariable analysis, low cognitive score and need for skill remediation, but not instruction method, impacted CPR skill performance. Conclusions HCP in resource-limited settings resuscitate frequently, with little CPR training. Using existing training, HCP acquire and retain skills, yet often require remediation. Novel techniques with increased student: instructor ratio and feedback manikins were not different compared to traditional instruction

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.</p

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase

Malaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism

Effect of mattress deflection on CPR quality assessment for older children and adolescents

Appropriate chest compression (CC) depth is associated with improved CPR outcome. CCs provided in hospital are often conducted on a compliant mattress. The objective was to quantify the effect of mattress compression on the assessment of CPR quality in children. Methods: A force and deflection sensor (FDS) was used during CPR in the Pediatric Intensive Care Unit and Emergency Department of a children's hospital. The sensor was interposed between the chest of the patient and hands of the rescuer and measured CC depth. Following CPR event, each event was reconstructed with a manikin and an identical mattress/backboard/patient configuration. CCs were performed using FDS on the sternum and a reference accelerometer attached to the spine of the manikin, providing a means to Calculate the mattress deflection. Results: Twelve CPR events with 14,487 CC (11 patients, median age 14.9 years) were recorded and reconstructed: 9 on ICU beds (9296 CC), 3 on stretchers (5191 CC). Measured mean CC depth during CPR was 47 +/- 8 mm on ICU beds, and 45 +/- 7 mm on stretcher beds with overestimation of 13 +/- 4 mm and 4 +/- 1 mm, respectively, due to mattress compression. After adjusting for this, the proportion of CC that met the CPR guidelines decreased from 88.4 to 31.8% on ICU beds (p < 0.001), and 86.3 to 64.7% on stretcher (p < 0.001 The proportion of appropriate depth CC was significantly smaller on ICU beds (p < 0.001). Conclusion: CC conducted on a non-rigid surface may not be deep enough. FDS may overestimate CC depth by 28% on ICU beds, and 10% on stretcher beds

Video performance-debriefings and ventilation-refreshers improve quality of neonatal resuscitation

Aim: Providers caring for newly born infants require skills and knowledge to initiate prompt and effective positive pressure ventilation (PPV) if the newborn does not breathe spontaneously after birth. We hypothesized implementation of high frequency/short duration deliberate practice training and post event video-based debriefings would improve process of care and decreases time to effective spontaneous respiration. Methods: Pre- and post-interventional quality study performed at two Norwegian university hospitals. All newborns receiving PPV were prospectively video-recorded, and initial performance data guided the development of educational interventions. A priori primary outcome was changed from process of care using the Neonatal Resuscitation Performance Evaluation (NRPE) score to time to effective spontaneous respiration as the NRPE score could only be obtained from one site due to lack of staff resources. Results: Over 12 months, 297 PPV-Refreshers and 52 performance debriefings were completed with 227 unique providers attending a PPV-Refresher and 93 unique providers completed a debriefing. We compared 102 PPV-events pre- to 160 PPV-events post-bundle implementation. The time to effective spontaneous respiration decreased from median (95% confidence interval) 196 (140–237) to 144 (120–163) s, p = 0.010. The NRPE-score increased significantly from median 77% (75–81) pre- to 89% (86–92) post-implementation, p 100 beats/min or number of newborns transferred to intensive care. Conclusion: High frequency/short duration deliberate practice PPV psychomotor training combined with performance-focused team debriefings using video recordings of actual resuscitations may improve time to effective spontaneous breathing and adherence to guidelines during real neonatal resuscitations