Quantification of neonatal procedural pain severity: a platform for estimating total pain burden in individual infants.

There is increasing evidence that long-term outcomes for infants born prematurely are adversely affected by repeated exposure to noxious procedures. These interventions vary widely, for example, in the extent of damage caused and duration. Neonatal intensive care unit (NICU) procedures are therefore likely to each contribute differently to the overall pain burden of individual neonates, ultimately having a different impact on their development. For researchers to quantify the procedural pain burden experienced by infants on NICU, we aimed to estimate the pain severity of common NICU procedures using published pain scores. We extracted pain scores over the first minute (pain reactivity) from the literature, using 59 randomized controlled trials for 15 different procedures. Hierarchical cluster analysis of average pain scores resulted in 5 discrete severity groups; mild (n = 1), mild to moderate (n = 3), moderate (n = 7), severe (n = 3), and very severe (n = 1). The estimate of the severity of individual procedures provided new insight into infant pain reactivity which is not always directly related to the invasiveness and duration of a procedure; thus, both heel lance and skin tape removal are moderately painful procedures. This estimate of procedural pain severity, based on pain reactivity scores, provides a novel platform for retrospective quantification of an individual neonate's pain burden due to NICU procedures. The addition of measures that reflect the recovery from each procedure, such as brain activity and behavioural regulation, would further improve estimates of the pain burden of neonatal intensive care.

Paramedic attitudes and experiences of enrolling patients into the PARAMEDIC-2 adrenaline trial: a qualitative survey within the London Ambulance Service.

OBJECTIVES: The aim of this study was to gather the views and experiences of paramedics who participated in a large-scale randomised controlled drug trial and to identify barriers to recruitment. DESIGN: We surveyed paramedics using a questionnaire consisting of a mix of closed and open ended questions. SETTING: The study was conducted within the London Ambulance Service, London, UK. PARTICIPANTS: 150 paramedics who were trained to enrol patients into the PARAMEDIC-2 randomised controlled trial of adrenaline versus placebo in out-of-hospital cardiac arrest and who returned the questionnaire. RESULTS: 98% of study participants felt prehospital research was very important, and 97.3% reported an overall positive experience of being involved in a drug trial. Only 5.3% felt uncomfortable enrolling patients into the trial without prior consent from the patient or a relative. Over one- third (39.3%) identified one or more barriers to patient recruitment, the most common being the attitudes of other staff. CONCLUSION: We found a strong appetite for involvement in prehospital research among paramedics and an understanding of the importance of research that prevailed over the complexities of the trial. This is an important finding demonstrating that potentially ethically controversial research can be undertaken successfully by paramedics in the prehospital environment.

Repeated adrenaline doses and survival from an out-of-hospital cardiac arrest.

BACKGROUND: Adrenaline is the primary drug of choice for resuscitation from out-of-hospital cardiac arrest (OHCA). Although adrenaline may increase the chance of achieving return of spontaneous circulation (ROSC), there is limited evidence that repeated doses of adrenaline improves overall survival, and increasing evidence of a detrimental effect on neurological function in survivors. This paper reports the relationship between repeated doses of adrenaline and survival in a cohort of patients attended by the London Ambulance Service in the United Kingdom. METHODS: A retrospective review of OHCA treated by the London Ambulance Service over a one year period. Patients aged ≥18 years who received one or more doses of adrenaline (1 mg bolus) during resuscitation were included in the analyses. Outcomes described are survival to hospital discharge and survival to one year post-arrest. RESULTS: Over the one year study period, 3151 patients received adrenaline during OHCA. A significant inverse relationship was found between increasing cumulative doses of adrenaline and survival both to hospital discharge and one year post-arrest. No patients survived after receiving more than ten adrenaline doses. CONCLUSION: Our study indicates that repeated doses of adrenaline are associated with decreasing odds of survival. There were no survivors amongst patients requiring more than 10 doses of adrenaline.

Calcium-activated SK channels control firing regularity by modulating sodium channel availability in midbrain dopamine neurons.

Dopamine neurons in the substantia nigra pars compacta and ventral tegmental area regulate behaviours such as reward-related learning, and motor control. Dysfunction of these neurons is implicated in Schizophrenia, addiction to drugs, and Parkinson's disease. While some dopamine neurons fire single spikes at regular intervals, others fire irregular single spikes interspersed with bursts. Pharmacological inhibition of calcium-activated potassium (SK) channels increases the variability in their firing pattern, sometimes also increasing the number of spikes fired in bursts, indicating that SK channels play an important role in maintaining dopamine neuron firing regularity and burst firing. However, the exact mechanisms underlying these effects are still unclear. Here, we develop a biophysical model of a dopamine neuron incorporating ion channel stochasticity that enabled the analysis of availability of ion channels in multiple states during spiking. We find that decreased firing regularity is primarily due to a significant decrease in the AHP that in turn resulted in a reduction in the fraction of available voltage-gated sodium channels due to insufficient recovery from inactivation. Our model further predicts that inhibition of SK channels results in a depolarisation of action potential threshold along with an increase in its variability.