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A retrospective nationwide study on the use of intravenous (IV) zanamivir in patients receiving intensive care who were pretreated with oseltamivir in the Netherlands was performed. In 6 of 13 patients with a sustained reduction of the viral load, the median time to start IV zanamivir was 9 days (range, 4-11 days) compared with 14 days (range, 6-21 days) in 7 patients without viral load reduction (P = .052). Viral load response did not influence mortality. We conclude that IV zanamivir as late add-on therapy has limited effectiveness. The effect of an immediate start with IV zanamivir monotherapy or in combination with other drugs need to be evaluated. [ABSTRACT FROM AUTHOR]

Background: The likelihood of return of spontaneous circulation with conventional advanced life support is known to have an exponential decline and therefore neurological outcome after 20 min in patients with a cardiac arrest is poor. Initiation of venoarterial ExtraCorporeal Membrane Oxygenation (ECMO) during resuscitation might improve outcomes if used in time and in a selected patient category. However, previous studies have failed to significantly reduce the time from cardiac arrest to ECMO flow to less than 60 min. We hypothesize that the initiation of Extracorporeal Cardiopulmonary Resuscitation (ECPR) by a Helicopter Emergency Medical Services System (HEMS) will reduce the low flow time and improve outcomes in refractory Out of Hospital Cardiac Arrest (OHCA) patients., Methods: The ON-SCENE study will use a non-randomised stepped wedge design to implement ECPR in patients with witnessed OHCA between the ages of 18-50 years old, with an initial presentation of shockable rhythm or pulseless electrical activity with a high suspicion of pulmonary embolism, lasting more than 20, but less than 45 min. Patients will be treated by the ambulance crew and HEMS with prehospital ECPR capabilities and will be compared with treatment by ambulance crew and HEMS without prehospital ECPR capabilities. The primary outcome measure will be survival at hospital discharge. The secondary outcome measure will be good neurological outcome defined as a cerebral performance categories scale score of 1 or 2 at 6 and 12 months., Discussion: The ON-SCENE study focuses on initiating ECPR at the scene of OHCA using HEMS. The current in-hospital ECPR for OHCA obstacles encompassing low survival rates in refractory arrests, extended low-flow durations during transportation, and the critical time sensitivity of initiating ECPR, which could potentially be addressed through the implementation of the HEMS system. When successful, implementing on-scene ECPR could significantly enhance survival rates and minimize neurological impairment., Trial Registration: Clinicaltyrials.gov under NCT04620070, registration date 3 November 2020., (© 2024. The Author(s).)

Introduction: Quality improvement in prehospital emergency medical services (EMS) can only be achieved by high-quality research and critical appraisal of current practices. This study examines current opportunities and barriers in EMS research in the Netherlands., Methods: This mixed-methods consensus study consisted of three phases. The first phase consisted of semi-structured interviews with relevant stakeholders. Thematic analysis of qualitative data derived from these interviews was used to identify main themes, which were subsequently discussed in several online focus groups in the second phase. Output from these discussions was used to shape statements for an online Delphi consensus study among relevant stakeholders in EMS research. Consensus was met if 80% of respondents agreed or disagreed on a particular statement., Results: Forty-nine stakeholders participated in the study; qualitative thematic analysis of the interviews and focus group discussions identified four main themes: (1) data registration and data sharing, (2) laws and regulations, (3) financial aspects and funding, and (4) organization and culture. Qualitative data from the first two phases of the study were used to construct 33 statements for an online Delphi study. Consensus was reached on 21 (64%) statements. Eleven (52%) of these statements pertained to the storage and use of EMS patient data., Conclusion: Barriers for prehospital EMS research in the Netherlands include issues regarding the use of patient data, privacy and legislation, funding and research culture in EMS organizations. Opportunities to increase scientific productivity in EMS research include the development of a national strategy for EMS data and the incorporation of EMS topics in research agendas of national medical professional associations., (© 2023. The Author(s).)

Introduction: In mechanically ventilated adults, thickening fraction of diaphragm (dTF) measured by ultrasound is used to predict extubation success. Whether dTF can also predict extubation success in children is unclear., Aim: To investigate the association between dTF and extubation success in children. Second, to assess diaphragm thickness during ventilation and the correlation between dTF, diaphragm thickness (Tdi), age and body surface., Method: Prospective observational cohort study in children aged 0-18 years old with expected invasive ventilation for >48 h. Ultrasound was performed on day 1 after intubation (baseline), day 4, day 7, day 10, at pre-extubation, and within 24 h after extubation. Primary outcome was the association between dTF pre-extubation and extubation success. Secondary outcome measures were Tdi end-inspiratory and Tdi end-expiratory and atrophy defined as <10% decrease of Tdi end-expiratory versus baseline at pre-extubation. Correlations were calculated with Spearman correlation coefficients. Inter-rater reliability was calculated with intraclass correlation (ICC)., Results: Fifty-three patients, with median age 3.0 months (IQR 0.1-66.0) and median duration of invasive ventilation of 114.0 h (IQR 55.5-193.5), were enrolled. Median dTF before extubation with Pressure Support 10 above 5 cmH 2 O was 15.2% (IQR 9.7-19.3). Extubation failure occurred in six children, three of whom were re-intubated and three then received non-invasive ventilation. There was no significant association between dTF and extubation success; OR 0.33 (95% CI; 0.06-1.86). Diaphragmatic atrophy was observed in 17/53 cases, in three of extubation failure occurred. Children in the extubation failure group were younger: 2.0 months (IQR 0.81-183.0) vs. 3.0 months (IQR 0.10-48.0); p  = 0.045. At baseline, pre-extubation and post-extubation there was no significant correlation between age and BSA on the one hand and dTF, Tdi- insp and Tdi-exp on the other hand. The ICC representing the level of inter-rater reliability between the two examiners performing the ultrasounds was 0.994 (95% CI 0.970-0.999). The ICC of the inter-rater reliability between the raters in 36 paired assessments was 0.983 (95% CI 0.974-0.990)., Conclusion: There was no significant association between thickening fraction of the diaphragm and extubation success in ventilated children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Duyndam, Smit, Houmes, Heunks, Molinger, IJland, van Rosmalen, Van Dijk, Tibboel and Ista.)

Background: Sparse data are available on prehospital care by Helicopter Emergency Medical Service (HEMS) for pediatric patients with traumatic brain injury (TBI). This study focusses on prehospital interventions, neurosurgical interventions and mortality in this group., Methods: We performed a retrospective analysis of pediatric (0-18 years of age) patients with TBI treated by Rotterdam HEMS., Results: From January 2012 to December 2017 415 pediatric (<18 years of age) patients with TBI were included. Intubation was required in in 92 of 111 patients with GCS ≤ 8, 92 (82.9%), compared to 12 of 77 (15.6%) with GCS 9-12, and 7 of 199 (3.5%) with GCS 13-15. Hyperosmolar therapy (HSS) was started in 73 patients, 10 with a GCS ≤8. Decompressive surgery was required in 16 (5.8%), nine patients (56.3%) of these received HSS from HEMS. Follow-up data was available in 277 patients. A total of 107 (38.6%) patients were admitted to a (P)ICU. Overall mortality rate was 6.3%(n = 25) all with GCS ≤8, 15 (60.0%) died within 24 hours and 24 (96.0%) within a week. Patients with neurosurgical interventions (N = 16) showed a higher mortality rate (18.0%)., Conclusions: The Dutch HEMS provides essential emergency care for pediatric TBI patients, by performing medical procedures outside of regular EMS protocol. Mortality was highest in patients with severe TBI (n = 111) (GCS≤8) and in those who required neurosurgical interventions. Despite a relatively good initial GCS (>8) score, there were patients who required prehospital intubation and HSS. This group will require further investigation to optimize care in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Oude Alink et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The first-pass success rate for endotracheal intubation (ETI) depends on provider experience and exposure. We hypothesize that video laryngoscopy (VL) improves first-pass and overall ETI success rates in low and intermediate experienced airway providers and prevents from unrecognized oesophageal intubations in prehospital settings., Methods: In this study 3632 patients were included. In all cases, an ambulance nurse, HEMS nurse, or HEMS physician performed prehospital ETI using direct Laryngoscopy (DL) or VL., Results: First-pass ETI success rates for ambulance nurses with DL were 45.5% (391/859) and with VL 64.8% (125/193). For HEMS nurses first-pass success rates were 57.6% (34/59) and 77.2% (125/162) respectively. For HEMS physicians these successes were 85.9% (790/920) and 86.9% (1251/1439). The overall success rate for ambulance nurses with DL was 58.4% (502/859) and 77.2% (149/193) with VL. HEMS nurses successes were 72.9% (43/59) and 87.0% (141/162), respectively. HEMS physician successes were 98.7% (908/920) and 99.0% (1425/1439), respectively. The incidence of unrecognized intubations in the oesophagus before HEMS arrival in traumatic circulatory arrest (TCA) was 30.6% with DL and 37.5% with VL. In medical cardiac arrest cases the incidence was 20% with DL and 0% with VL., Conclusion: First-pass and overall ETI success rates for ambulance and HEMS nurses are better with VL. The used device does not affect success rates of HEMS physicians. VL resulted in less unrecognized oesophageal intubations in medical cardiac arrests. In TCA cases VL resulted in more oesophageal intubations when performed by ambulance nurses before HEMS arrival., (© 2022. The Author(s).)

Background: In prehospital care, the Helicopter Emergency Medical Service (HEMS) can be dispatched for critically injured or ill children. However, little detail is known about dispatches for children, in terms of the incidence of prehospital interventions and overall mortality. The primary objective of this study is to provide an overview of pediatric patient characteristics and incidence of interventions., Methods: A retrospective chart review of all patients ≤ 17 years who received medical care by Rotterdam HEMS from 2012 until 2017 was carried out., Results: During the study period, 1905 pediatric patients were included. 59.1% of patients were male and mean age was 6.1 years with 53.2% of patients aged ≤ 3 years. 53.6% were traumatic patients and 49.7% were non-traumatic patients. 18.8% of patients were intubated. Surgical procedures were performed in 0.9%. Medication was administered in 58.1% of patients. Cardiopulmonary resuscitation (CPR) was necessary in 12.9% of patients, 19.9% were admitted to the intensive care unit and 14.0% needed mechanical ventilation. Overall mortality was 9.5%. Mortality in trauma patients was 5.5% and in non-trauma group 15.3%. 3.9% of patients died at the scene., Conclusions: Patients attended by HEMS are at high risk of prehospital interventions like CPR or intubation. EMS has little exposure to critically ill or injured children. Hence, HEMS expertise is required to perform critical procedures. Trauma patients had higher survival rates than non-traumatic patients. This may be explained by underlying illnesses in non-traumatic patients and CPR as reason for dispatch. Further research is needed to identify options for improving prehospital care in the non trauma pediatric patients., (© 2021. The Author(s).)

Objective: There is generally limited but conflicting literature on the incidence, causes, and outcomes of pediatric out-of-hospital cardiac arrest. This study was performed to determine the incidence and outcome of pediatric out-of-hospital cardiac arrest reported by all helicopter emergency medical services in the Netherlands and to provide a description of causes and treatments and, in particular, a description of the specific interventions that can be performed by a physician-staffed helicopter emergency medical service., Methods: A retrospective analysis was performed of all documented pediatric (0 < 18 years of age) out-of-hospital cardiac arrests from July 2015 to July 2017, attended by all 4 Dutch helicopter emergency medical service teams., Results: Two hundred two out-of-hospital cardiac arrests were identified. The overall incidence in the Netherlands is 3.5 out-of-hospital cardiac arrests in children per 100,000 pediatric inhabitants. The overall survival rate for out-of-hospital cardiac arrest was 11.4%. Eleven (52%) of the survivors were in the drowning group and between 12 and 96 months of age., Conclusion: Helicopter emergency medical services are frequently called to pediatric out-of-hospital cardiac arrests in the Netherlands. The survival rate is normal to high compared with other countries. The 12- to 96-month age group and drowning seem to have a relatively favorable outcome., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/purpose: Coagulation complications are frequent, unwanted occurrences in extracorporeal membrane oxygenation (ECMO) treatment, possibly influenced by the pump in the ECMO-circuit. We hypothesized that fewer complications would occur with a smaller, heparin-coated ECMO system with a centrifugal pump (CP) than with one with a roller pump (RP) and that after conversion, complication rates would decrease over time., Methods: This single-center, retrospective chart study included all first neonatal and pediatric ECMO runs between 2009 and 2015. Differences between groups were assessed with Mann-Whitney U tests and Kruskal-Wallis tests. Determinants of complication rates were evaluated through Poisson regression models. The CP group was divided into three consecutive groups to assess whether complication rates decreased over time., Results: The RP group comprised 90 ECMO runs and the CP group 82. Hemorrhagic complication rates were significantly higher with the CP than with the RP, without serious therapeutic consequences, while thrombotic complications rates were unaffected. Intracranial hemorrhage rates and coagulation-related mortality rates were similar. Gained experience with the CP did not improve complication rates or survival over time., Conclusions: Although the CP seems safe, it does not seem beneficial over the RP. Further research is warranted on how pump type affects coagulation, taking into account the severity and implications of coagulation complications., Level of Evidence: Level III., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: The quality of resuscitation and effective leadership are decisive for the outcome of a resuscitation. Nurses are usually the first responders upon cardiac arrest. Therefore, we started the "proficiency check" project, which aims to improve nurses' resuscitation and teamwork skills. This article describes the effectiveness of the proficiency check and nurses' experiences with it., Design and Methods: This study was done among intensive care nurses working on a pediatric ICU (PICU) in the Netherlands. It was designed as a mixed-methods study combining a quantitative and a qualitative approach. Quantitative data were obtained through a pre-posttest comparison of nurses' resuscitation and teamwork skills, in a simulation setting. Qualitative data on nurses' experiences were collected through semi-structured individual interviews., Results: Both resuscitation and teamwork skills improved significantly. In 39 nurses (32%), the improvement of both resuscitation and teamwork skills after the intervention was large (effect size >0.8). The experiences of nurses regarding the proficiency check were diverse: on the positive side, increased knowledge and confidence were reported, whereas negative experiences related, among other things, to stress and anxiety., Conclusions: Resuscitation and teamwork skills of PICU nurses can be enhanced by the 'proficiency check' studied here. This simulation-based training can be further improved by incorporating the nurses' experiences., Practice Implications: A simulation-based assessment for resuscitation may play an important role in a PICU, and possibly for other skills and in other settings as well. Particular attention should be paid to the stress that many nurses experience due to skills assessment., Competing Interests: Declaration of Competing Interest None of the authors has any conflict of interest to disclose. No external funding has been received. All authors have approved the manuscript and agree with its submission to the Journal of Pediatric Nursing., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Emergency medical service (EMS) is responsible for prehospital care encompassing all ages, irrespective of injury cause or medical condition, which includes peripartum emergencies. When patients require care more advanced than the level provided by the national EMS protocol, an EMS physician-staffed Dutch helicopter emergency medical service (HEMS) may be dispatched. In the Netherlands in 2016, there were 21.434 planned home births guided by midwives alone without further obstetric assistance, accounting for 12.7% of all births that year. However, there are no clear data available thus far regarding neonates requiring emergency care with or without HEMS assistance. This article reviews neonates during our study period who received medical care after birth by HEMS., Methods: A retrospective chart review was performed including neonates born on the day of the dispatch between January 2012 and December 2017 who received additional medical care from the Rotterdam HEMS., Results: Fifty-two neonates received medical care by HEMS. The majority (73.1%) were full-term (Gestational age > 37 weeks). Home delivery was intended in 63.5%, 20% of whom experienced an uncomplicated delivery but had a poor start of life. The majority of unplanned deliveries (n = 17) were preterm (70.6%). Two were born by resuscitative hysterotomy; 1 survived in good neurologic condition, and the other died at the scene. Fifteen neonates (28.9%) required cardiopulmonary resuscitation; in 2 cases, no resuscitation was started on medical grounds, and 12 of the other 13 resuscitated neonates regained return of spontaneous circulation. In 33 (63.5%) of the neonates, respiratory interventions were required; 8 (15.4%) were intubated before transport. Death was confirmed in 5 (9.6%) neonates, all preterm., Conclusion: During the study period, 52 neonates required medical assistance by HEMS. The 5 infants who died were all preterm. In this cohort, adequate basic life support was implemented immediately after birth either by the attending midwife, EMS, or HEMS on arrival. This suggests that prehospital first responders know the basic skills of neonatal life support., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Critically ill children treated with invasive mechanical ventilation in a paediatric intensive care unit (PICU) may suffer from complications leading to prolonged duration of ventilation and PICU stay., Objective: The objective of this study is to find out if the use of a nurse-driven ventilation weaning protocol in a PICU can shorten the duration of mechanical ventilation., Methods: In a prospective, pretest-posttest implementation study, we implemented a nurse-driven ventilation weaning protocol and compared its outcomes with those of the usual physician-driven weaning. In the posttest period, nurses weaned the patients until extubation as per this protocol. The primary outcome was duration of ventilation. The secondary outcomes were length of PICU stay, reintubation rate, and compliance with the protocol (measured by use of the prescribed support mode)., Results: In total, 424 patients aged from 0 to 18 years (212 pretest and 212 posttest) were included; in both groups, the median age was 3 months. The median duration of ventilation did not differ significantly between the pretest and posttest periods: 42.5 h. (interquartile range, IQR 14.3-121.3) vs. 44.5 h (IQR 12.3-107.0), respectively; p = 0.589. In the posttest period, the PICU stay was nonsignificantly shorter: 5.5 days (IQR 2-11) vs. 7 days (IQR 3-14) in the pretest period; p = 0.432. Compliance with the prescribed support mode was significantly higher in the posttest period: 69.9% vs. 55.7% in the pretest period; p = 0.005. The reintubation rate was not significantly different between the pretest and posttest periods (5% vs. 7%, respectively; p = 0.418). The extubation rate during nights was higher in the posttest period but not significantly different (p = 0.097)., Conclusions: Implementation of a nurse-driven weaning protocol did not result in a significantly shorter duration of invasive mechanical ventilation but was safe and successful. The reintubation rate did not significantly increase compared with usual care., (Copyright © 2019 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Extracorporeal membrane oxygenation (ECMO) treatment alleviates systemic cardiorespiratory failure. However, it is unclear whether ECMO also improves microcirculatory function, as the microcirculation can be disturbed despite normal systemic hemodynamics. We therefore aimed to study the sublingual microcirculation (SMC) throughout neonatal and pediatric ECMO treatment. We hypothesized that the SMC improves after starting ECMO, that the SMC differs between venovenous (VV) and venoarterial (VA) ECMO, and that insufficient recovery of microcirculatory disturbances during ECMO predicts mortality. Methods: This single-center prospective longitudinal observational study included 34 consecutive children (April 2016-September 2018). The SMC was assessed daily with a handheld vital microscope (integrated with incident dark field illumination) before, during, and after ECMO. Validated parameters of vessel density, perfusion, and flow quality were assessed for all vessels (diameter <100 μm) and small vessels (<20 μm). Linear mixed models and logistic regression models were built to assess changes over time and identify significant covariates. Using ROC curves, the predictive values of microcirculatory parameters were assessed for mortality on ECMO and overall mortality. Results: The study population comprised 34 patients (median age 0.27 years, 16 neonates, 16 females). Twelve patients were treated with VV and 22 with VA ECMO. Twelve patients died during ECMO (stopped due to futility) and 3 died after ECMO but before discharge. Microcirculatory parameters did not change significantly before, during or after ECMO. Except between microcirculatory flow index (MFI) and mean arterial pressure (MAP), no significant associations were found between microcirculatory parameters and global systemic hemodynamics. The probability of an undisturbed MFI (>2.6) increased with higher MAP (OR: 1.050, 95%CI: 1.008-1.094). Microcirculatory parameters did not significantly differ between VV and VA ECMO or between survivors and non-survivors. None of the microcirculatory parameters could predict mortality on ECMO or overall mortality. Conclusion: In this heterogeneous study population, we were not able to demonstrate an effect of ECMO on the sublingual microcirculation. Microcirculatory parameters did not change throughout ECMO treatment and did not differ between VV and VA ECMO or between survivors and non-survivors. Future research should focus on determining which neonatal and pediatric ECMO patients would benefit from microcirculatory monitoring and how.

Objectives: The role of venoarterial extracorporeal membrane oxygenation in the treatment of severe pediatric septic shock continues to be intensely debated. Our objective was to determine whether the use of venoarterial extracorporeal membrane oxygenation in severe septic shock was associated with altered patient mortality, morbidity, and/or length of ICU and hospital stay when compared with conventional therapy., Design: International multicenter, retrospective cohort study using prospectively collected data of children admitted to intensive care with a diagnosis of severe septic shock between the years 2006 and 2014., Setting: Tertiary PICUs in Australia, New Zealand, Netherlands, United Kingdom, and United States., Patients: Children greater than 30 days old and less than 18 years old., Interventions: None., Measurements and Main Results: Of 2,452 children with a diagnosis of sepsis or septic shock, 164 patients met the inclusion criteria for severe septic shock. With conventional therapy (n = 120), survival to hospital discharge was 40%. With venoarterial extracorporeal membrane oxygenation (n = 44), survival was 50% (p = 0.25; CI, -0.3 to 0.1). In children who suffered an in-hospital cardiac arrest, survival to hospital discharge was 18% with conventional therapy and 42% with venoarterial extracorporeal membrane oxygenation (Δ = 24%; p = 0.02; CI, 2.5-42%). Survival was significantly higher in patients who received high extracorporeal membrane oxygenation flows of greater than 150 mL/kg/min compared with children who received standard extracorporeal membrane oxygenation flows or no extracorporeal membrane oxygenation (82%, 43%, and 48%; p = 0.03; CI, 0.1-0.7 and p < 0.01; CI, 0.2-0.7, respectively). Lengths of ICU and hospital stay were significantly longer for children who had venoarterial extracorporeal membrane oxygenation., Conclusions: The use of venoarterial extracorporeal membrane oxygenation in severe pediatric sepsis is not by itself associated with improved survival. However, venoarterial extracorporeal membrane oxygenation significantly reduces mortality after cardiac arrest due to septic shock. Venoarterial extracorporeal membrane oxygenation flows greater than 150 mL/kg/min are associated with almost twice the survival rate of conventional therapy or standard-flow extracorporeal membrane oxygenation.

Objective: After severe (primary) brain injury, Dutch physician-based helicopter emergency medical services start therapy to lower the intracranial pressure (ICP) on scene to stop or delay secondary brain injury. In some cases, helicopter transportation to the nearest level 1 trauma center is indicated. During transportation, the head-down position may counteract the ICP-lowering strategies because of venous blood pooling in the head. To examine this theory, we measured the optic nerve sheath diameter (ONSD) during helicopter transport in healthy volunteers., Methods: The ONSD was measured by ultrasound in healthy volunteers during helicopter liftoff and acceleration in the supine position or with a raised headrest., Results: In this proof-of-principle study, the ONSD increased during helicopter acceleration (-9° Trendelenburg, mean = 5.6 ± .3 mm) from baseline (0° supine position, mean = 5.0 ± .4 mm). After headrest elevation (20°-25°), the ONSD did not increase during helicopter acceleration (mean ONSD = 5.0 ± .5 mm)., Conclusion: ONSD and ICP seem to increase during helicopter transportation in -9° head-down (Trendelenburg) position. By raising the headrest of the gurney before liftoff, these effects can be prevented., (Copyright © 2018 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Since the introduction of extracorporeal membrane oxygenation (ECMO), more neonates and children with cardiorespiratory failure survive. Interest has therefore shifted from reduction of mortality toward evaluation of long-term outcomes and prevention of morbidity. This review addresses the changes in ECMO population and the ECMO-treatment that may affect long-term outcomes, the diagnostic modalities to evaluate neurological morbidities and their contributions to prognostication of long-term outcomes. Most follow-up data have only become available from observational follow-up programs in neonatal ECMO-survivors. The main topics are discussed in this review. Recommendations for long-term follow up depend on the presence of neurological comorbidity, the nature and extent of the underlying disease, and the indication for ECMO. Follow up should preferably be offered as standard of care, and in an interdisciplinary, structured and standardized way. This permits evaluation of outcome data and effect of interventions. We propose a standardized approach and recommend that multiple domains should be evaluated during long-term follow up of neonates and children who needed extracorporeal life support.

Technological innovations in pediatric extracorporeal life support circuits can reduce system-related complications and may improve patients' outcome. The Deltastream DP3 (Medos Medizintechnik AG, Stolberg, Germany) is a novel rotational pump with a diagonally streamed impeller that can be used over a broad range of flows. We collected patient data from seven pediatric centers to conduct a retrospective cohort study. We examined 233 patients whose median age was 1.9 (0-201) months. The DP3 system was used for cardiopulmonary support as veno-arterial extracorporeal membrane oxygenation (ECMO) in 162 patients. Respiratory support via veno-venous ECMO was provided in 63 patients. The pump was used as a ventricular assist device in eight patients. Median supporting time was 5.5 (0.2-69) days and the weaning rate was 72.5%. The discharge home rate was 62% in the pulmonary group versus 55% in the cardiac group. Extracorporeal cardiopulmonary resuscitation was carried out in 24 patients (10%) with a survival to discharge of rate of 37.5%. About 106 (47%) children experienced no complications, while 33% suffered bleeding requiring blood transfusion or surgical intervention. Three patients suffered a fatal cerebral event. Renal replacement therapy was performed in 28% and pump or oxygenator exchange in 26%. Multivariable analysis identified system exchange (OR 1.94), kidney failure (OR 3.43), and complications on support (OR 2.56) as risk factors for dismal outcome. This novel diagonal pump has demonstrated its efficacy in all kinds of mechanical circulatory and respiratory support, revealing good survival rates., (© 2017 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

Background: Open lung biopsy can help differentiate between reversible and irreversible lung disease and may guide therapy. To assess the risk-benefit ratio of this procedure in pediatric extracorporeal membrane oxygenation (ECMO) patients, we reviewed data of all patients who underwent an open lung biopsy during ECMO in one of the two pediatric ECMO centers in a nationwide study in the Netherlands., Results: In nineteen neonatal and six pediatric patients (0-15.5years), twenty-five open lung biopsies were performed during the study period. In 13 patients (52%), a classifying diagnosis of underlying lung disease could be made. In another nine patients (36%), specific pathological abnormalities were described. In three patients (12%), only nonspecific abnormalities were described. The histological results led to withdrawal of ECMO treatment in 6 neonates with alveolar capillary dysplasia/misalignment of pulmonary veins (24%) and in another 6 patients, corticosteroids were started (24%). All patients survived the biopsy procedure. Hemorrhagic complications were rare., Conclusion: An open lung biopsy during an ECMO run in neonates and children is a safe procedure with a minimum risk for blood loss and biopsy-related death. It can be very useful in diagnosing the underlying pathology and can guide cessation of ECMO treatment and thereby avoid continuation of futile treatment, especially in neonatal patients., Level of Evidence: III., Type of Study: Diagnostic study., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In October 2016, a severe infection with swine influenza A(H1N1) virus of the Eurasian avian lineage occurred in a child with a previous history of eczema in the Netherlands, following contact to pigs. The patient's condition deteriorated rapidly and required life support through extracorporeal membrane oxygenation. After start of oseltamivir treatment and removal of mucus plugs, the patient fully recovered. Monitoring of more than 80 close unprotected contacts revealed no secondary cases., (This article is copyright of The Authors, 2016.)

Aims and Objectives: To evaluate to what extent physicians on a paediatric intensive care unit (PICU) adhered to a newly implemented ventilation algorithm., Background: PICUs worldwide use different ventilators with a wide variety of ventilation modes. We developed an algorithm, as part of a larger protocol, for choice of ventilation mode at time of admission., Design: This study was performed in a level III PICU of a university children's hospital and had an uncontrolled, pre-post test design with a period before implementation (T0) and two periods after implementation (T1 and T2)., Methods: An invasive ventilation algorithm targeted at two patient groups was implemented in October 2008. The algorithm distinguished between lung disease, in which pressure control was considered as the preferred mode, and no lung disease, in which pressure-regulated volume control was preferred. Nurses and physicians were instructed in the use of the algorithm before implementation., Results: During three test periods, a total of 507 children with a median age of 5 months [interquartile range (IQR) 0-50] on conventional invasive mechanical ventilation were included. In patients with lung disease, pre-implementation adherence rate was 79% (67/85). At T1 it was 71% (51/72); at T2 84% (46/55). The slight improvement from T1 to T2 was statistically not significant (p = 0·092). In patients with no lung disease, the adherence rate rose statistically significantly from 66% at T0 (62/93) to 78% (79/101) at T1, and 84% at T2 (85/101) (p = 0·015)., Conclusion: Implementation of a new ventilation algorithm increased physicians' adherence to this ventilation algorithm and the effect was sustained over time. This was achieved by education, reminders and organizational changes such as admission of postcardiac surgery patients with protocolized nursing care including preset ventilator settings., Relevance to Clinical Practice: Interdisciplinary collaboration, effective communication, leadership support and organizational aspects may be effective strategies to improve adherence to protocols., (© 2014 British Association of Critical Care Nurses.)

Background: Dynamic arterial lactate indices predict mortality more accurately than static arterial lactate measurements in children with septic shock or congenital cardiac defects. The current study evaluates whether this also applies to children with primary respiratory disease requiring extracorporeal membrane oxygenation (ECMO)., Methods: Static arterial lactate levels (LACabs) were prospectively collected before and during ECMO support for this single center, observational cohort study. Also, time-weighted arterial lactate (LACtw) and lactate change over time (LACdelta) were calculated as dynamic indices for, respectively, the duration and the trend over time of lactate derangement. Intensive care mortality was the primary endpoint. Analyses were performed for neonatal and pediatric patients separately., Results: Fifty-six neonatal and 39 pediatric patients were included. Eighteen (32%) neonatal and 12 (31%) pediatric patients died. The evolution of LACabs and LACdelta differed between the pediatric survivors and the pediatric non-survivors (P<0.001, P=0.025). The hazard ratio was 1.23 (CI95=1.06-1.43, P=0.007) for LACabs and 20.64 (CI95=1.99-214.20, P=0.011) for LACdelta, indicating that higher lactate levels increase the risk for mortality. The predictive value for LACabs was 0.75 (CI95=0.57-0.93) and for LACdelta 0.69 (CI95=0.51-0.87), respectively. There were neither consistent differences for LACtw in the pediatric patients, nor for any of the static or dynamic lactate indices in the neonatal patients., Conclusion: Static arterial lactate measurements and, to a lesser extent, dynamic arterial lactate indices predict mortality in pediatric, but not neonatal ECMO patients. The magnitude and trend over time rather than the duration of lactate derangement are associated with mortality.

Objective: To determine the prevalence of and to classify ultrasound-proven brain injury during neonatal extracorporeal membrane oxygenation in The Netherlands., Design: Retrospective nationwide study (Rotterdam and Nijmegen), spanning two decades., Setting: Level III university hospitals., Subjects: All neonates who underwent neonatal extracorporeal membrane oxygenation from 1989 to 2010., Interventions: None., Measurements and Main Results: Cranial ultrasound images were reviewed independently by two investigators without knowledge of primary diagnosis, outcome, type of extracorporeal membrane oxygenation, or statistics. The scans were reviewed for lesion type and timing, with the use of a refined classification method for focal brain injury. Extracorporeal membrane oxygenation type was venoarterial in 88%. Brain abnormalities were detected in 17.3%: primary hemorrhage was most frequent (8.8%). Stroke was identified in 5% of the total group, with a notable significant preference for the left hemisphere (in 70%). Lobar hematoma (prevalence 2.2 %) was also significantly left predominant., Conclusion: The incidence of brain injury found with cranial ultrasound in The Netherlands of the patients treated with extracorporeal membrane oxygenation during the neonatal period was 17.3%. Primary hemorrhage was the largest group of lesions, not clearly side-specific except for lobar bleeding, most probably related to changes in venous flow. Arterial ischemic stroke occurred predominant in the left hemisphere.

This review will address the different challenges for the use of non-neonatal extracorporeal membrane oxygenation (ECMO). It will discuss the available evidence for the use of pediatric ECMO in respiratory and circulatory failure, focusing on indications and contra-indications and choice of ECMO mode. Furthermore we will try to define optimal treatment goals, identify primary outcome parameters and calculate the expected need for non-neonatal ECMO per 1.000.000 inhabitants.

ECMO support is an established life saving therapy for potentially reversible respiratory and/or cardiac failure. Improvement of outcome depends on effective treatment of the primary diagnosis and complications. Adequate drug therapy is important in reaching these goals. Pharmacokinetic and pharmacodynamic data in neonates and older children on ECMO are sparse. Most studies show altered volume of distribution and clearance for the drugs studied. This article gives an overview of the available PK and PD studies in neonates and children on ECMO, suggests possible mechanisms of altered PK and PD and identifies areas of interest for further research.

Background: Congenital diaphragmatic hernia (CDH) can be repaired on or off extracorporeal membrane oxygenation (ECMO). In many centers, operating off ECMO is advocated to prevent bleeding complications. We aimed to compare surgery-related bleeding complications between repair on or off ECMO., Methods: All patients with CDH repair and ECMO treatment between January 1, 1995, and May 31, 2008, were retrospectively reviewed. Tranexamic acid was routinely given to all patients repaired on ECMO for 24 hours perioperatively after 2003. Extra-fluid expansion, transfusion, or relaparotomy caused by postoperative bleeding were scored as surgery-related bleeding complications and were related to the Extracorporeal Life Support Organization (ELSO) registry. We used χ(2) test and t test for statistics., Results: Demographic data and surgery-related bleeding complications in the on-ECMO group were not significantly different compared with the off-ECMO group (P = .331) in our institute. In contrast, more surgery-related bleeding complications were reported by ELSO in their on-ECMO group (P < .0001)., Conclusion: In contrast to the data from the ELSO registry, we did not observe significantly more surgery-related bleeding complications after CDH repair on ECMO. Using a specific perioperative hemostatic treatment enabled us to perform CDH repair on ECMO with a low frequency of bleeding complications, thereby taking advantage of having the physiologic benefits of ECMO available perioperatively., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The purpose of the present study was to critically review the existing body of evidence on ventilation modes for infants and children up to the age of 18 years., Methods: The PubMed and EMBASE databases were searched using the search terms 'artificial respiration', 'instrumentation', 'device', 'devices', 'mode', and 'modes'. The review included only studies comparing two ventilation modes in a randomized controlled study and reporting one of the following outcome measures: length of ventilation (LOV), oxygenation, mortality, chronic lung disease and weaning. We quantitatively pooled the results of trials where suitable., Results: Five trials met the inclusion criteria. They addressed six different ventilation modes in 421 children: high-frequency oscillation (HFO), pressure control (PC), pressure support (PS), volume support (VS), volume diffusive respirator (VDR) and biphasic positive airway pressure. Overall there were no significant differences in LOV and mortality or survival rate associated with the different ventilation modes. Two trials compared HFO versus conventional ventilation. In the pooled analysis, the mortality rate did not differ between these modes (odds ratio = 0.83, 95% confidence interval = 0.30 to 1.91). High-frequency ventilation (HFO and VDR) was associated with a better oxygenation after 72 hours than was conventional ventilation. One study found a significantly higher PaO2/FiO2 ratio with the use of VDR versus PC ventilation in children with burns. Weaning was studied in 182 children assigned to either a PS protocol, a VS protocol or no protocol. Most children could be weaned within 2 days and the weaning time did not significantly differ between the groups., Conclusions: The literature provides scarce data for the best ventilation mode in critically ill children beyond the newborn period. There is no evidence, however, that high-frequency ventilation reduced mortality and LOV. Longer-term outcome measures such as pulmonary function, neurocognitive development, and cost-effectiveness should be considered in future studies.

Purpose: In most extracorporeal membrane oxygenation (ECMO) centers patients are heavily sedated to prevent accidental decannulation and bleeding complications. In ventilated adults not on ECMO, daily sedation interruption protocols improve short- and long-term outcome. This study aims to evaluate safety and feasibility of sedation interruption following cannulation in neonates on ECMO., Methods: Prospective observational study in 20 neonates (0.17-5.8 days of age) admitted for ECMO treatment. Midazolam (n = 20) and morphine (n = 18) infusions were discontinued within 30 min after cannulation. Pain and sedation were regularly assessed using COMFORT-B and visual analog scale (VAS) scores. Midazolam and/or morphine were restarted and titrated according to protocolized treatment algorithms., Results: Median (interquartile range, IQR) time without any sedatives was 10.3 h (5.0-24.1 h). Median interruption duration for midazolam was 16.5 h (6.6-29.6 h), and for morphine was 11.2 h (6.7-39.4 h). During this period no accidental extubations, decannulations or bleeding complications occurred., Conclusions: This is the first study to show that interruption of sedatives and analgesics following cannulation in neonates on ECMO is safe and feasible. Interruption times are 2-3 times longer than reported for adult ICU patients not on ECMO. Further trials are needed to substantiate these findings and evaluate short- and long-term outcomes.

'Acute respiratory distress syndrome' (ARDS) developed as a serious complication of an infection with the influenza virus A (H1N1) ('swine flu') in 3 children: a 15-year-old girl, a 6-year-old boy and a 14-year-old girl. The latter two patients also suffered from septic shock. Intensive ICU treatment, including mechanical ventilation, did not lead to recovery. The first two patients eventually recovered following treatment with extracorporeal membrane oxygenation (ECMO), but the third patient's condition was too unstable for transfer to an ECMO centre. This patient died.

'Acute respiratory distress syndrome' (ARDS) developed as a serious complication of an infection with the influenza virus A (H1N1) ('swine flu') in 3 children: a 15-year-old girl, a 6-year-old boy and a 14-year-old girl. The latter two patients also suffered from septic shock. Intensive ICU treatment, including mechanical ventilation, did not lead to recovery. The first two patients eventually recovered following treatment with extracorporeal membrane oxygenation (ECMO), but the third patient's condition was too unstable for transfer to an ECMO centre. This patient died.

Background: This study was undertaken to investigate the effect of a small dose of perfluorocarbon on the recruitment pressure needed to open atelectatic lung areas., Methods: In 12 Yorkshire pigs (body weight, 9 kg), lung injury was induced by whole lung lavage. After 1 h of conventional ventilation, an open lung maneuver was performed to obtain PaO2 values equal to the pre-lavage PaO2 values (+/-10%). After 1 h of ventilation at the lowest possible airway pressure that stabilized the recruited lung volume, the animals were disconnected from the ventilator to allow the lung to collapse. Six animals received a 5 ml/kg intratracheal dose of perfluorocarbon and a second open lung maneuver was performed. Six animals served as controls and received no perfluorocarbon but also underwent a second open lung maneuver., Results: In both groups, an open lung maneuver resulted in a significant increase in oxygenation. The peak pressures needed to open the lung after 1 h of mechanical ventilation in the perfluorocarbon and control groups were 43.8 +/- 8.4 cmH2O and 46.6 +/- 4 cmH2O, respectively. The addition of perfluorocarbon significantly reduced the opening pressure to 34.5 +/- 6.3 cmH2O (P < 0.01), whereas the opening pressure in the control group, 45.0 +/- 0.2 cmH2O, did not change., Conclusion: The instillation of a small amount of perfluorocarbon significantly reduces the opening pressures needed to recruit atelectatic lung areas.

Introduction: Loop diuretics are the most frequently used diuretics in patients treated with extracorporeal membrane oxygenation (ECMO). In patients after cardiopulmonary bypass (CPB) surgery, the use of continuous furosemide infusion is increasingly documented. Because ECMO and CPB are 'comparable' procedures, continuous furosemide infusion is used in newborns on ECMO. We report on the use of continuous intravenous furosemide in neonates treated with ECMO., Methods: This was a retrospective observational study in neonates treated with continuous intravenous furosemide during ECMO., Results: Thirty-one patients were included in the study. A median of 25 (9-149) hours after the start of ECMO, continuous furosemide therapy was started at a median rate of 0.08 (0.02-0.17) mg/kg per hour. The continuous furosemide dose was not changed in the individual patient. Seven patients received a furosemide bolus prior to, and five patients received additional loop diuretics during, the continuous infusion. Urine production before continuous furosemide therapy was not significantly different between patients who received a furosemide bolus prior to the infusion and those who did not receive this bolus (P = 0.2879). Although a positive effect of the 'loading' bolus was observed in urine output in the first 24 hours, there was no statistically significant difference in urine output (P = 0.0961) or in time (P = 0.1976) to reach a urine output of 6 ml/kg per hour between patients. After 24 hours, urine production remained a median of 6.2 ml/kg per hour irrespective of furosemide boluses. The forced diuresis was well tolerated as illustrated by stable haemodynamic parameters and a decrease in ECMO flow and vasopressor score over the observation period., Conclusion: This is the first report on continuous intravenous furosemide therapy in newborns treated with ECMO. The furosemide regimens used in this study varied widely in continuous and intermittent doses. However, all regimens achieved adequate urine output. An advantage of continuous, over intermittent, intravenous furosemide could not be documented. Furosemide dosing regimens should be developed for neonates treated with ECMO. In addition, therapeutic drug-monitoring studies are required to prevent furosemide toxicity because so far no data are available on serum furosemide levels in neonates treated with ECMO.

Background: After alarming reports concerning deaths after sedation with propofol, infusion of this drug was contraindicated by the US Food and Drug Administration in children <18 yr receiving intensive care. We describe our experiences with propofol 6%, a new formula, during postoperative sedation in non-ventilated children following craniofacial surgery., Methods: In a prospective cohort study, children admitted to the paediatric surgical intensive care unit following major craniofacial surgery were randomly allocated to sedation with propofol 6% or midazolam, if judged necessary on the basis of a COMFORT behaviour score. Exclusion criteria were respiratory infection, allergy for proteins, propofol or midazolam, hypertriglyceridaemia, familial hypercholesterolaemia or epilepsy. We assessed the safety of propofol 6% with triglycerides (TG) and creatine phosphokinase (CPK) levels, blood gases and physiological parameters. Efficacy was assessed using the COMFORT behaviour scale, Visual Analogue Scale and Bispectral Index monitor., Results: Twenty-two children were treated with propofol 6%, 23 were treated with midazolam and 10 other children did not need sedation. The median age was 10 (IQR 3-17) months in all groups. Median duration of infusion was 11 (range 6-18) h for propofol 6% and 14 (range 5-17) h for midazolam. TG levels remained normal and no metabolic acidosis or adverse events were observed during propofol or midazolam infusion. Four patients had increased CPK levels., Conclusion: We did not encounter any problems using propofol 6% as a sedative in children with a median age of 10 (IQR 3-17) months, with dosages <4 mg kg(-1) h(-1) during a median period of 11 (range 6-18) h.

A 33-year-old woman was trapped in a car following an accident. Because of her size (241 kg; BMI: 85 kg/m2) it was difficult to free, transport, examine and treat her. A few days after she had been discharged with a knee injury, she was again admitted for pneumonia. Partly as a result of para-infectious rhabdomyolysis, she died 5 days later. More and more people in The Netherlands are overweight, and more and more often to an extreme degree. Complicated accident kinetics, problems with diagnosis and treatment, comorbidity and an increased risk of complications in obese patients contribute to the poorer prognosis following blunt trauma. It is therefore practically impossible to give obese patients the usual care according to the protocol. Adaptations like positioning in the anti-Trendelenburg, left lateral-tilt position, as well as bigger and stronger equipment, may improve the care of trauma patients with morbid obesity.

Objective: To assess the effects of increasing concentrations of inhaled nitric oxide (NO) during incremental dosages of partial liquid ventilation (PLV) on gas exchange, hemodynamics, and oxygen transport in pigs with induced acute lung injury (ALI)., Design: Prospective experimental study., Setting: Experimental intensive care unit of a university., Subjects: 6 pigs with induced ALI., Interventions: Animals were surfactant-depleted by lung lavage to a partial pressure of oxygen in arterial blood (PaO2) < 100 mmHg. They then received four incremental doses of 5 ml/kg perflubron (Liqui-Vent). Between each dose the animals received 0, 10, 20, 30, 40, and 0 parts per million (ppm) NO., Measurements and Main Results: Blood gases, hemodynamic parameters, and oxygen delivery were measured after each dose of perflubron as well as after each NO concentration. Perflubron resulted in a dose-dependent increase in PaO2. At each perflubron dose, additional NO inhalation resulted in a further significant (ANOVA, p < 0.05) increase in PaO2, with a maximum effect at 30 +/- 10 ppm NO. The 5 ml/kg perflubron dose led to a significant decrease in mean pulmonary artery pressure, which decreased further with higher NO concentrations., Conclusions: PLV can be combined with NO administration and results in a cumulative effect on arterial oxygenation and to a decrease in pulmonary artery pressure, without having any deleterious effect on measured systemic hemodynamic parameters.

Objectives: To investigate the effects of partial liquid ventilation (i.e., mechanical ventilation in combination with intratracheal administration of perfluorocarbon) on lung function, with particular attention to the integrity of the alveolocapillary membrane in healthy adult animals., Design: Prospective, randomized, controlled study., Setting: Laboratory at the Department of Experimental Anesthesiology, Erasmus University Rotterdam., Subjects: Ten adult male New Zealand rabbits., Interventions: Five rabbits were intratracheally treated with 12 mL/kg of perfluorocarbon while conventional mechanical ventilation (volume-controlled, tidal volume of 12 mL/kg, respiratory rate of 30 breaths/min, inspiration/expiration ratio of 1:2, positive end-expiratory pressure of 2 cm H2O, and an FIO2 of 1.0) was applied for 3 hrs. To assess the permeability of the alveolocapillary membrane, pulmonary clearance of inhaled technetium-99m-labeled diethylenetriamine pentaacetic acid (99mTc-DTPA) measurements were performed at 3 hrs and compared with data from the control group (n = 5) treated with mechanical ventilation only, using the same ventilatory parameters., Measurements and Main Results: Pulmonary gas exchange and lung mechanical parameters were measured in both groups at 30-min intervals. Mean values for PaO2 in the perfluorocarbon group, although at adequate levels, were less than those values of the control group during the 3-hr study period (370 +/- 44 vs. 503 +/- 44 torr at 3 hrs [49.3 +/- 5.9 vs. 67.1 +/- 5.9 kPa]). Peak and mean airway pressures were higher in the perfluorocarbon group (ranging from 1.9 to 3.4 cm H2O and 0.7 to 1.3 cm H2O, respectively) compared with the control group, while end-inspiratory airway pressure was similar in both groups. The half-life of 99mTc-DTPA was 83.7 +/- 24.5 mins in the control group, which was significantly longer (p < .01) than in the perfluorocarbon group (49.8 +/- 6.1 mins)., Conclusions: These findings suggest that partial liquid ventilation with perfluorocarbons lowers pulmonary gas exchange in healthy animals, and the increased pulmonary clearance of 99mTc-DTPA after 3 hrs of this type of ventilatory support may reflect minimal reversible changes in the lung surfactant system.

Objective: To assess the effect of partial liquid ventilation with perfluorocarbons on hemodynamics and gas exchange in large pigs with induced acute lung injury (ALI)., Design: Randomized, prospective, double-control, experimental study. Experimental intensive care unit of a university., Materials: Eighteen large pigs (50 +/- 5 kg body weight) with an average anterior posterior thoracic diameter of 24 cm and induced acute lung injury., Interventions: All animals were surfactant depleted by lung lavage to a PaO2 below 100 mmHg and randomized to receive either perflubron (n = 6) or saline (n = 6) in five intratracheal doses of 5 ml/kg at 20-min intervals, or no instillation (n = 6)., Measurements and Results: In all animals heart rate, arterial pressures, pulmonary pressures, cardiac output and blood gases were recorded at 20-min intervals. There was no deleterious effect on any hemodynamic parameter in the perflubron group, whereas systolic and mean pulmonary arterial pressure values showed a persistent decrease after the first 5 ml/kg of perflubron, from 48.7 +/- 14.1 to 40.8 +/- 11.7 mmHg and from 39.7 +/- 13.2 to 35.2 +/- 12.0 mmHg, respectively. Perflubron resulted in a significant (ANOVA P < 0.01), dose-dependent increase in PaO2 values from 86.3 +/- 22.4 to a maximum of 342.4 +/- 59.4 mmHg at a dose of 25 ml/kg; the other groups showed no significant increase in PaO2., Conclusions: Tracheal instillation of perflubron in induced ALI results in a dose-dependent increase in PaO2 and has no deleterious effect on hemodynamic parameters.

This study was designed to determine the relative analgesic efficacy and safety of single intramuscular injections of ketorolac (10 mg or 30 mg) and morphine (10 mg) in patients of either sex with moderate to severe pain after major surgery. In a single-dose, randomised, double-blind study of parallel design, pain was assessed immediately before injection of test medication and at regular intervals for 8 h thereafter. One hundred and seventeen patients (109 undergoing cardiac surgery; 8 lung surgery) were randomized to one of the three treatment groups. Pain intensity was assessed using a 5-point verbal scale before administration of study drugs. Postadministration, at 30 min and hourly for 8 h, pain intensity and pain relief were assessed, again using the 5-point verbal scale. Additionally, as a measure of analgesia, forced expiratory volume (FEV1) was obtained in all patients. Vital signs including blood pressure, pulse, temperature, respiratory rate and blood gases (PaCO2) were recorded prior to and after study medication. Based on hourly pain intensity differences and hourly pain relief observations, ketorolac 10 mg was generally more effective than morphine 10 mg, and ketorolac 30 mg was generally more effective than ketorolac 10 mg. The results of this study show that ketorolac is an effective and safe (with regard to arterial pressure, blood gases and lung function) analgesic for relief of postoperative pain after major surgery in stable patients. No clinically significant adverse effects occurred during the study. One cannot exclude an influence on patients with organ system dysfunction or on parameters not measured in this study.

The analgesic efficacy and safety of tramadol and morphine were compared in a double-blind, randomized study of 150 female patients after gynecologic surgery. As required, patients could receive up to three intravenous doses of either 50 mg of tramadol or 5 mg of morphine within a period of 6 h. Pain intensity (verbal response score) was recorded before injection and at 0.5, 1, 2, 3, 5, and 6 h after the initial dose; at these times, pain relief was also assessed. Oxygen saturation was monitored continuously by pulse oximetry for at least 30 min after each injection. In 13.3% of the morphine group (but in none of the tramadol group) transcutaneous pulse oxygen saturation decreased to less than 86%; in 50% of these patients the decrease occurred after only the first 5 mg of morphine. Both drugs produced acceptable analgesia, and there were no clinically significant adverse events. In demonstrating the absence of clinically relevant respiratory depression with tramadol, we underline its safety for postoperative pain relief.