Implementation of an algorithm for tapering analgosedation reduces iatrogenic withdrawal syndrome in pediatric intensive care.

BACKGROUND: Proper analgosedation is a cornerstone in the treatment of critically ill patients in Pediatric Intensive Care Units (PICUs). Medications, such as fentanyl, morphine, and midazolam, are essential to safe and respectful care. The use of these medications over time may lead to side effects such as iatrogenic withdrawal syndrome (IWS) in the tapering phase. The aim of the study was to test an algorithm for tapering analgosedation to reduce the prevalence of IWS in two Norwegian PICUs at Oslo University Hospital. METHODS: A cohort of mechanically ventilated patients from newborn to 18 years with continuous infusions of opioids and benzodiazepines for 5 days or more were included consecutively from May 2016 to December 2021. A pre- and posttest design, with an intervention phase using an algorithm for tapering analgosedation after the pretest, was used. The ICU staffs were trained in using the algorithm after the pretest. The primary outcome was a reduction in IWS. The Withdrawal Assessment Tool-1 (WAT-1) was used to identify IWS. A WAT-1 score ≥3 indicates IWS. RESULTS: We included 80 children, 40 in the baseline group, and 40 in the intervention group. Age and diagnosis did not differ between the groups. The prevalence of IWS was 95% versus 52.5% in the baseline group versus the intervention group, and the peak WAT-1 median was 5.0 (IQR 4-6.8) versus 3.0 (IQR 2.0-6.0) (p = .012). Based on SUM WAT-1 ≥ 3, which describes the burden over time better, we demonstrated a reduction of IWS, from a median of 15.5 (IQR 8.25-39) to a median of 3 (IQR 0-20) (p = <.001). CONCLUSION: We suggest using an algorithm for tapering analgosedation in PICUs since the prevalence of IWS was significantly lower in the intervention group in our study.

Outcome in Children Admitted to the First PICU in Malawi.

OBJECTIVES: Dedicated PICUs are slowly starting to emerge in sub-Saharan Africa. Establishing these units can be challenging as there is little data from this region to inform which populations and approaches should be prioritized. This study describes the characteristics and outcome of patients admitted to the first PICU in Malawi, with the aim to identify factors associated with increased mortality. DESIGN: Review of a prospectively constructed PICU database. Univariate analysis was used to assess associations between demographic, clinical and laboratory factors, and mortality. Univariate associations ( p < 0.1) for mortality were entered in two multivariable models. SETTING: A recently opened PICU in a public tertiary government hospital in Blantyre, Malawi. PATIENTS: Children admitted to PICU between August 1, 2017, and July 31, 2019. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Of 531 included PICU admissions, 149 children died (28.1%). Mortality was higher in neonates (88/167; 52.7%) than older children (61/364; 16.8%; p ≤ 0.001). On univariate analysis, gastroschisis, trachea-esophageal fistula, and sepsis had higher PICU mortality, while Wilms tumor, other neoplasms, vocal cord papilloma, and foreign body aspiration had higher survival rates compared with other conditions. On multivariable analysis, neonatal age (adjusted odds ratio [AOR], 4.0; 95% CI, 2.0-8.3), decreased mental state (AOR, 5.8; 95 CI, 2.4-13.8), post-cardiac arrest (AOR, 2.0; 95% CI, 1.0-8.0), severe hypotension (AOR, 6.3; 95% CI, 2.0-19.1), lactate greater than 5 mmol/L (AOR, 4.2; 95% CI, 1.5-11.2), pH less than 7.2 (AOR, 3.1; 95% CI, 1.2-8.0), and platelets less than 150 × 10 9 /L (AOR, 2.4; 95% CI, 1.1-5.2) were associated with increased mortality. CONCLUSIONS: In the first PICU in Malawi, mortality was relatively high, especially in neonates. Surgical neonates and septic patients were identified as highly vulnerable, which stresses the importance of improvement of PICU care bundles for these groups. Several clinical and laboratory variables were associated with mortality in older children. In neonates, severe hypotension was the only clinical variable associated with increased mortality besides blood gas parameters. This stresses the importance of basic laboratory tests, especially in neonates. These data contribute to evidence-based approaches establishing and improving future PICUs in sub-Saharan Africa.

Increasing burden of viral bronchiolitis in the pediatric intensive care unit; an observational study.

PURPOSE: Viral bronchiolitis is a major cause of pediatric intensive care unit (PICU) admission. Insight in the trends of bronchiolitis-associated PICU admissions is limited, but imperative for future PICU resource and capacity planning. MATERIALS AND METHODS: We retrospectively studied trends in PICU admissions for bronchiolitis in six European sites, including three full national registries, between 2000 and 2019 and calculated population-based estimates per 100,000 children where appropriate. Information concerning risk factors for severe disease and use of invasive mechanical ventilation was also collected when available. RESULTS: In total, there were 15,606 PICU admissions for bronchiolitis. We observed an increase in the annual number, rate and estimates per 100,000 children of PICU admissions for bronchiolitis at all sites over the last two decades, while the proportion of patients at high risk for severe disease remained relatively stable. CONCLUSIONS: The international increased burden of bronchiolitis for the PICU is concerning, and warrants further international attention and investigation.

Iatrogenic withdrawal syndrome frequently occurs in paediatric intensive care without algorithm for tapering of analgosedation.

BACKGROUND: Analgesics and sedatives are key elements to reduce physiological and psychological stress associated with treatment in paediatric intensive care. Prolonged drug use may induce tolerance and development of iatrogenic withdrawal syndrome (IWS) during the tapering phase. Our primary aim was to describe the prevalence of IWS among critically ill ventilated patients in two Norwegian paediatric intensive care units (PICUs), and secondary to investigate what motivated bedside nurses to administer additional drug doses. METHODS: Mechanically ventilated patients (n = 40) from newborn to eighteen years of age, with continuous infusions of opioids and benzodiazepines for 5 days or more, were included consecutively from May 2016 to June 2018. By using Withdrawal Assessment Tool-1 (WAT-1) twice daily we recorded the prevalence of IWS. Additionally, we recorded signs and symptoms that led bedside nurses to administration extra bolus medication. RESULTS: Peak WAT-1 score indicated an IWS prevalence of 95% in this selected group. The first days of the tapering phase were most critical for IWS. The most frequent symptoms triggering administration of additional bolus doses were agitation/restlessness, and thiopental and propofol were the bolus drugs used most frequently. CONCLUSIONS: IWS affected 95% of the children having received infusions of opioids and benzodiazepines for 5 days or more in PICUs without a tapering protocol for these drugs. This calls for implementation and testing of such weaning protocols.

Transpulmonary thermodilution (PiCCO) measurements in children without cardiopulmonary dysfunction: large interindividual variation and conflicting reference values.

BACKGROUND: The PiCCO system, based on transpulmonary thermodilution, is one of the few tools available for continuous hemodynamic monitoring in children. However, published data for some of the derived variables reveal indexed values that seem questionable. AIMS: The aim of this study was to collect data from hemodynamically normal children and compare these to existing reference values. Furthermore, we sought to explore if indexing some of the variables differently could improve the clinical application of the obtained values. METHODS: This is a prospective observational study in a tertiary university hospital including 31 children without cardiopulmonary disease scheduled for major neurosurgery. Measurements were performed after induction of general anesthesia. RESULTS: Median age was 8 months. PiCCO-derived median Cardiac Index (CI) was 3.8 l · min(-1) · m(-2) (range 2.6-6.6), reference range 3.0-5.0, median Global End-Diastolic Volume Index (GEDVI) was 366 ml · m(-2) (range 269-685), reference range 680-800, whereas median Extravascular Lung Water Index (EVLWI) was 12 ml · kg(-1) (range 7-31), reference range 3-7. All measured variables had a high interindividual variation, especially in children weighing less than 15 kg. CONCLUSIONS: Values obtained by the PiCCO system in children have a wide range, and should therefore be interpreted with caution. Current reference values published for GEDVI and EVLWI are not applicable in children; the former is too high and the latter too low, and should not guide clinical practice. Indexing by other physiological indices may reduce this problem. Using current variables, we find GEDVI 280-590 ml · m(-2) and ELWI 7-27 ml · kg(-1) to be typical ranges for children.

Pressure-derived versus pressure wave amplitude-derived indices of cerebrovascular pressure reactivity in relation to early clinical state and 12-month outcome following aneurysmal subarachnoid hemorrhage.

OBJECT: Indices of cerebrovascular pressure reactivity (CPR) represent surrogate markers of cerebral autoregulation. Given that intracranial pressure (ICP) wave amplitude-guided management, as compared with static ICP-guided management, improves outcome following aneurysmal subarachnoid hemorrhage (SAH), indices of CPR derived from pressure wave amplitudes should be further explored. This study was undertaken to investigate the value of CPR indices derived from static ICP-arterial blood pressure (ABP) values (pressure reactivity index [PRx]) versus ICP-ABP wave amplitudes (ICP-ABP wave amplitude correlation [IAAC]) in relation to the early clinical state and 12-month outcome in patients with aneurysmal SAH. METHODS: The authors conducted a single-center clinical trial enrolling patients with aneurysmal SAH. The CPR indices of PRx and IAAC of Week 1 after hemorrhage were related to the early clinical state (Glasgow Coma Scale [GCS] score) and 12-month outcome (modified Rankin Scale score). RESULTS: Ninety-four patients were included in the study. The IAAC, but not the PRx, increased with decreasing GCS score; that is, the higher the IAAC, the worse the clinical state. The PRx could differentiate between survivors and nonsurvivors only, whereas the IAAC clearly distinguished the groups "independent," "dependent," and "dead." In patients with an average IAAC ≥ 0.2, mortality was approximately 3-fold higher than in those with an IAAC < 0.2. CONCLUSIONS: The IAAC, which is based on single ICP-ABP wave identification, relates significantly to the early clinical state and 12-month outcome following aneurysmal SAH. Impaired cerebrovascular pressure regulation during the 1st week after a bleed relates to a worse outcome. CLINICAL TRIAL REGISTRATION NO.: NCT00248690.

A randomized and blinded single-center trial comparing the effect of intracranial pressure and intracranial pressure wave amplitude-guided intensive care management on early clinical state and 12-month outcome in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND: In patients with aneurysmal subarachnoid hemorrhage (SAH), preliminary results indicate that the amplitude of the single intracranial pressure (ICP) wave is a better predictor of the early clinical state and 6-month outcome than the mean ICP. OBJECTIVE: To perform a randomized and blinded single-center trial comparing the effect of mean ICP vs mean ICP wave amplitude (MWA)-guided intensive care management on early clinical state and outcome in patients with aneurysmal SAH. METHODS: Patients were randomized to 2 different types of ICP management: maintenance of mean ICP less than 20 mm Hg and MWA less than 5 mm Hg. Early clinical state was assessed daily using the Glasgow Coma Scale. The primary efficacy variable was 12-month outcome in terms of the Rankin Stroke Score. RESULTS: Ninety-seven patients were included in the study. There were no significant differences in treatment between the 2 groups apart from a larger volume of cerebrospinal fluid drained during week 1 in the MWA group. There was a tendency toward higher Glasgow Coma Scale scores in the MWA group during weeks 1 (P = .08) and 2 (P = .07). Outcome in terms of Rankin Stroke Score at 12 months was significantly better in the MWA group (P < .05). CONCLUSION: This randomized and blinded trial disclosed a significant better primary efficacy variable (Rankin Stroke Score after 12 months) in the MWA patient group. We suggest that proactive intensive care management with MWA-tailored cerebrospinal fluid drainage during the first week improves aneurysmal SAH outcome.

Differential effects of osmotherapy on static and pulsatile intracranial pressure.

OBJECTIVE: A bolus infusion of 7.2% saline in 6% hydroxyethyl starch 200/0.5 (HS) attenuates static intracranial pressure (mean ICP) in subarachnoid hemorrhage patients. This study addressed how HS affects intracranial pulsatility, which is more indicative of intracranial compliance than static ICP. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Intensive care unit in a university hospital. PATIENTS: Sedated and mechanically ventilated patients suffering from spontaneous subarachnoid hemorrhage. INTERVENTIONS: Twenty patients received an infusion of HS, mean 1.5 mL/kg. Static ICP was characterized by mean ICP and intracranial pulsatility by mean ICP wave amplitude, both parameters determined simultaneously during consecutive 6-sec time windows. We compared average values of these parameters during 15-min periods just before the infusion and after maximum effect was reached. MEASUREMENTS AND MAIN RESULTS: Mean ICP wave amplitude decreased 3.4 mm Hg from a baseline of 9.8 mm Hg, p < 0.0001. However, even though a target level of <15 mm Hg was reached for mean ICP in 65% of interventions, the target of <5 mm Hg for mean ICP wave amplitude was reached in only 30% of interventions. We found no correlation between changes in mean ICP wave amplitude and mean systemic arterial blood pressure wave amplitude, p = 0.27. CONCLUSIONS: The results confirm that osmotherapy attenuates both static ICP (mean ICP) and pulsatile ICP (mean ICP wave amplitude). Most importantly, however, during the majority of HS infusions, the target value of mean ICP wave amplitude was not reached even though the targets for mean ICP and mean cerebral perfusion pressure were reached. This suggests that the intracranial compliance state was still unfavorable even though mean ICP and mean cerebral perfusion pressure had reached normal ranges. The reduction in intracranial pulsatility could not be explained by attenuation in arterial pulsatility because there was no correlation between ICP and arterial blood pressure wave amplitudes.

Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamics in a placebo-controlled study involving stable patients with subarachnoid hemorrhage.

OBJECTIVE: To compare the effects of a bolus infusion of hypertonic saline hydroxyethyl starch with the effects of normal saline (placebo) on intracranial pressure (ICP) and cerebral perfusion pressure in patients with spontaneous subarachnoid hemorrhage. DESIGN AND SETTING: Prospective, randomized, single-blinded, placebo-controlled study in a university hospital. PATIENTS: A total of 22 mechanically ventilated patients with spontaneous subarachnoid hemorrhage with stable ICP between 10 and 20 mm Hg. INTERVENTIONS: During the course of 30 mins, 2 mL/kg of either 7.2% saline in 6% hydroxyethyl starch 200/0.5 (HSS) or of normal saline was infused. The effects were observed for another 180 mins. MEASUREMENTS AND MAIN RESULTS: Mean change in ICP after intervention (DeltaICP) calculated from the average of all observations was -3.3 (sd 2.6) mm Hg in the HSS group vs. -0.3 (sd 1.3) mm Hg in the normal saline group. Mean difference between the groups (HSS - normal saline) was -3.0 mm Hg (95% confidence interval, -4.9 to -1.1; p = .004). Mean peak change after HSS was -5.6 (range, -0.8 to -12.2) mm Hg after 64 (range, 40 to 115) mins. Mean difference in cerebral perfusion pressure change between the groups (HSS - normal saline) was 5.4 mm Hg (95% confidence interval, 2.2 to 8.6; p = .002), and mean difference in cardiac index change, measured as the area under the curve for the whole study period, corresponded to 0.2 L.min.m (95% confidence interval, 0.03 to 0.4; p = .025). CONCLUSIONS: In this placebo-controlled study involving spontaneous subarachnoid hemorrhage patients with normal to moderately increased ICP, 2 mL/kg HSS reduced ICP and increased cerebral perfusion pressure significantly. Maximum effect was reached at twice the infusion time of 30 mins. There were also beneficial hemodynamic effects with increased cardiac index in the HSS group.

[A six-year-old girl with dyspnea following tracheocutaneous repair]. / En seks år gammel jente med dyspné etter operasjon på halsen.

BACKGROUND: A few patients develop prominent scars combined with persistent fistula after the removal of a long-standing tracheostomy tube. The procedure needed to correct the condition is generally considered minor surgery, normally without any significant complications. We describe, however, a patient who developed a particularly complicated postoperative course. MATERIAL AND METHODS: The patient was a six-year-old girl who underwent surgery because of significant scar formation and a persistent small tracheocutaneous fistula eight months after removal of the tube. Postoperatively she had a cough attack and developed spontaneously subcutaneous emphysema, pneumomediastinum and bilateral pneumothorax. She required intensive care, thoracic drainage and antibiotic prophylaxis. Over the next days her situation improved and she was discharged on the sixth day. INTERPRETATION: Operative treatment of scarring after tracheostomy in which the surgeon also confronts a tracheocutaneous fistula or an opening into the tracheal lumen requires postoperative observation so that any severe complications can be managed.

Universal fresh frozen plasma (Uniplas): a safe product in open-heart surgery.

OBJECTIVE: To test the tolerability and safety of the universal plasma Uniplas [solvent/detergent (SD)-treated plasma], infused regardless of the patient's blood group. DESIGN: Prospective, parallel group, controlled and observer-blinded study, randomized with respect to patients requiring plasma transfusion. SETTING: Cardiothoracic operating room and ICU in a university hospital. PATIENTS: Eighty-four patients undergoing open-heart surgery comparing three parallel treatment groups and one control group. INTERVENTIONS: The Uniplas treatment group was subdivided into patients with blood group A, B or AB, and group O. The treatment group receiving Octaplas of type AB, was not subdivided. Patients who did not require any plasma transfusion served as control. MEASUREMENTS: Complement activation (C3bc, TCC), direct antiglobulin test (DAT) and other immunohaematological tests, tests for haemolysis, and relevant clinical observations during treatment phase. Blood samples were collected again after 6 months for evaluation of viral safety. RESULTS: Of the 84 patients, 29 served as control group. Uniplas was transfused in 36 of the patients (1-23 units). Octaplas was transfused in 19 patients (1-11 units). During the study no clinical adverse events related to plasma transfusion were observed. The degree of complement activation C3bc and TCC, a recommended test for biocompatibility, did not show any increased activation after Uniplas or Octaplas transfusion. No haemolytic reactions, positive DAT-tests or viral transmissions were observed after Uniplas transfusion. CONCLUSION: In open-heart surgery, Uniplas, which can be transfused regardless of a patient's blood group, was well-tolerated and gave no adverse drug reactions.

Universal solvent/detergent-treated fresh frozen plasma (Uniplas--rationale and clinical properties.

Transfusions with incompatible blood products including plasma are a well-known problem. The present study was performed to test the effects of Uniplas, universal plasma that can be transfused regardless of a patient's blood group, with respect to bleeding and hemostatic activity. The study comprised 84 adult patients scheduled for elective openheart surgery. A total of 55 patients received plasma transfusions, while 29 patients not requiring plasma served as controls. If plasma transfusion was indicated during operation or over the two following days, patients were randomised 2:1 to receive Uniplas or Octaplas of blood group AB. Relevant clinical observations were recorded and blood tests taken repeatedly. The transfused patient groups were comparable, and no significant differences were observed with respect to activated clotting time (ACT), activated partial thromboplastin time (APTT) or postoperative bleeding into chest drains. The median number of transfused units of Uniplas was 3, with a range of 1-23, while the median for Octaplas was 2 with a range of 1-11. These differences were not significant.Thus, Uniplas has a similar effect as Octaplas in the treatment of bleeding in patients undergoing openheart surgery. Uniplas can therefore substitute for Octaplas and eliminate the risk of ABO-incompatible transfusions.