A Tale of 8 Cities: Pediatric Critical Care Redeployment to Adult Care During Wave 1 of COVID-19.

BACKGROUND: Pediatric hospital resources including critical care faculty (intensivists) redeployed to provide care to adults in adult ICUs or repurposed PICUs during wave 1 of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVES: To determine the magnitude of pediatric hospital resource redeployment and the experience of pediatric intensivists who redeployed to provide critical care to adults with COVID-19. METHODS: A mixed methods study was conducted at 9 hospitals in 8 United States cities where pediatric resources were redeployed to provide care to critically ill adults with COVID-19. A survey of redeployed pediatric hospital resources and semistructured interviews of 40 redeployed pediatric intensivists were simultaneously conducted. Quantitative data were summarized as median (interquartile range) values. RESULTS: At study hospitals, there was expansion in adult ICU beds from a baseline median of 100 (86-107) to 205 (108-250). The median proportion (%) of redeployed faculty (88; 66-100), nurses (46; 10-100), respiratory therapists (48; 18-100), invasive ventilators (72; 0-100), and PICU beds (71; 0-100) was substantial. Though driven by a desire to help, faculty were challenged by unfamiliar ICU settings and culture, lack of knowledge of COVID-19 and fear of contracting it, limited supplies, exhaustion, and restricted family visitation. They recommended deliberate preparedness with interprofessional collaboration and cross-training, and establishment of a robust supply chain infrastructure for future public health emergencies and will redeploy again if asked. CONCLUSIONS: Pediatric resource redeployment was substantial and pediatric intensivists faced formidable challenges yet would readily redeploy again.

Keto-Bezoar: Adverse Event Related to Initiation of Ketogenic Diet in an Infant.

The ketogenic diet is frequently used as part of the treatment regimen for pediatric patients with refractory epilepsy. This diet is generally well tolerated, with constipation being the most described side effect. This case highlights a previously undocumented severe complication of a "keto-bezoar" formation related to the initiation of the ketogenic diet in a young infant.

Practice Change From Intermittent Medication Boluses to Bolusing From a Continuous Infusion in Pediatric Critical Care: A Quality Improvement Project.

OBJECTIVES: To determine whether implementing a guideline to bolus medications from continuous infusions in PICUs affects nursing satisfaction, patient safety, central line entries, medication utilization, or cost. DESIGN: This is a pre- and postimplementation quality improvement study. SETTING: An 11-bed ICU and 14-bed cardiac ICU in a university-affiliated children's hospital. PATIENTS: Patients less than 18 years old admitted to the PICU or pediatric cardiac ICU receiving a continuous infusion of dexmedetomidine, midazolam, fentanyl, morphine, vecuronium, or cisatracurium from May 2015 to May 2016, excluding November 2015 (washout period), were eligible for inclusion. INTERVENTIONS: Change in practice from administering bolus doses from an automated dispensing machine to administering bolus medications from continuous infusion in PICUs. MEASUREMENTS AND MAIN RESULTS: Timing studies were conducted pre- and post implementation in 29 and 26 occurrences, respectively. The median time from the decision to give a bolus until it began infusing decreased by 169 seconds (p < 0.01). Nursing satisfaction increased from 19.3% pre- to 100% post implementation. Safety was assessed via barcode scanning compliance, which decreased by 1.4% for patients and 1% for medications, and smart pump limit overrides. The percentage of infusion pump bolus overrides increased as expected, with the majority (99%) of these exceeding soft maximum limits by less than two-fold. Central line entries were unaffected post implementation. To assess medication utilization, a total of 50 patients in each intervention group were selected for retrospective chart review. Daily fentanyl boluses increased from one to three (p = 0.021). However, midazolam infusion dose and fentanyl infusion duration decreased (p = 0.026 and p = 0.005, respectively). Medication utilization was otherwise unchanged post implementation (p > 0.05). Annualized cost avoidance was $124,160. CONCLUSIONS: Implementation of bolus medications from continuous infusion in PICUs significantly decreased time to begin a bolus dose and increased nursing satisfaction. The practice change also improved medication utilization without negatively impacting patient safety.

Alteplase infusion versus dwell for clearance of partially occluded central venous catheters in critically ill pediatric patients.

OBJECTIVE: To evaluate the efficacy and safety of alteplase infusions and alteplase local instillations (dwells) to clear partially occluded central venous catheters in critically ill children. DESIGN: Retrospective study. SETTING: PICU in a single, tertiary care, academic children's hospital. PATIENTS: Retrospective review of the medical records of all critically ill pediatric patients less than 18 years old who received an alteplase infusion or dwell as the treatment for a partial central venous catheter occlusion. The typical infusion regimen was to administer 0.1 mg/kg of body weight (maximum, 2 mg/dose) of alteplase in 25 mL of 0.9% sodium chloride over 3 hours. The standard dwell was to administer and aspirate alteplase in a 1 mg/mL concentration as a fixed dose as ordered by the prescriber (maximum, 2 mg/dose). Efficacy was defined as documentation of positive blood return from the catheter. Radiology reports, nursing and physician documentation, and laboratory values were reviewed to assess for bleeding events. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fifty occlusion events were included for analysis. Overall, 72 of 84 alteplase infusions (86%) and 53 of 66 alteplase dwells (80%) resulted in resolution of the lumen occlusion event as documented by positive blood return from the catheter after a maximum of two doses (p = 0.39). One major bleeding event occurred in each arm; both were deemed unlikely related to alteplase. CONCLUSIONS: Alteplase infusions to clear partially occluded central venous catheters appear to be as efficacious as alteplase dwells in critically ill children. In occlusions treated with an infusion, more occlusions resolved in older and larger patients and in patients with catheters in place less than 7 days. In occlusions treated with a dwell, more occlusions resolved in smaller catheters. The safety profile for both infusions and dwells was acceptable for the pediatric critically ill population.

Protein synthesis inhibition as a potential strategy for metabolic down-regulation.

OBJECTIVE: This pilot study tested the potential of puromycin (PUR) to inhibit protein synthesis and reduce oxygen utilization in a non-hibernating, whole animal preparation. METHODS: After anesthesia and instrumentation, male rats received a single dose of PUR or 0.9% saline (control), followed 60 min later with [(35)S] methionine/cysteine radiolabeling. Thirty minutes after isotope injection, organ biopsies were taken for quantification of de novo protein synthesis. Arterial and central venous blood gases were obtained at baseline and 60 min after injection of PUR or 0.9% saline. Temperature, mean arterial pressure (MAP), and heart rate were recorded continuously. RESULTS: Animals receiving PUR demonstrated significant reductions in protein synthesis in all organ systems sampled (p<0.05). The overall reduction averaged 67.8%. Central venous oxygen saturations (S(cv)O(2)) were higher in the PUR group than the controls at 60 min (90+/-2% versus 80+/-4%, p<0.05). The oxygen extraction ratio (O(2)ER) decreased from 16.1+/-1.7% to 6.8+/-1.2% in the PUR group (p<0.05) and increased from 12.5+/-3.2% to 16.0+/-4.2% in the controls (p=0.44). There was no difference in temperature, MAP, heart rate or blood gas variables, other than S(cv)O(2), at baseline or 60 min between groups. CONCLUSIONS: These results demonstrate that PUR is capable of reducing whole body protein synthesis significantly within a relatively short duration of time. This appears to decrease whole body oxygen utilization as evidenced by an increase in S(cv)O(2) and a decrease in O(2)ER. Protein synthesis inhibition may reduce metabolic demands and should be tested for its potential to improve outcomes where oxygen demands exceed oxygen delivery.

Convergence of Ca2+-desensitizing mechanisms activated by forskolin and phenylephrine pretreatment, but not 8-bromo-cGMP.

Contractile stimuli can sensitize myosin to Ca2+ by activating RhoA kinase (ROK) and PKC that inhibit myosin light chain phosphatase (MLCP) activity. Relaxant stimuli, acting through PKA and PKG (cyclic nucleotide-dependent protein kinases), and pretreatment with contractile agents such as phenylephrine (PE), can desensitize myosin to Ca2+. It is unknown precisely how these stimuli cause Ca2+ desensitization. To test the hypothesis that PKA, PKG, and PE pretreatment signaling systems converge to cause relaxation by inhibition of ROK in intact, isolated tissues, we examined the effects of forskolin (FSK; PKA activation), 8-bromo-cGMP (8br-cGMP; PKG activation), and PE pretreatment on KCl-induced force maintenance in rabbit arteries, a response nearly completely dependent on ROK activation. PE pretreatment and agents activating PKA and PKG caused Ca2+ desensitization by inhibiting KCl-induced tonic force and MLC phosphorylation without inhibiting intracellular [Ca2+]. At pCa 5 in beta-escin-permeabilized muscle, FSK and 8b-cGMP accelerated the relaxation rate when tissues were returned to pCa 9, suggesting that both agents can elevate MLCP activity. However, a component of the Ca2+ desensitization attributed to PKG activation in intact tissues appeared to involve a MLC phosphorylation-independent component. Inhibition of KCl-induced tonic force by the ROK inhibitor, Y-27632, and by PE pretreatment, were synergistically potentiated by 8b-cGMP, but not FSK. FSK and PE pretreatment, but not 8b-cGMP, inhibited the KCl-induced increase in site-specific myosin phosphatase target protein-1 phosphorylation at Thr853. These data support the hypothesis that PKA and PE pretreatment converge on a common Ca2+-desensitization pathway, but that PKG can act by a mechanism different from that activated by PKA and PE pretreatment.

Wound healing: an overview of acute, fibrotic and delayed healing.

Acute wounds normally heal in a very orderly and efficient manner characterized by four distinct, but overlapping phases: hemostasis, inflammation, proliferation and remodeling. Specific biological markers characterize healing of acute wounds. Likewise, unique biologic markers also characterize pathologic responses resulting in fibrosis and chronic non-healing ulcers. This review describes the major biological processes associated with both normal and pathologic healing. The normal healing response begins the moment the tissue is injured. As the blood components spill into the site of injury, the platelets come into contact with exposed collagen and other elements of the extracellular matrix. This contact triggers the platelets to release clotting factors as well as essential growth factors and cytokines such as platelet-derived growth factor (PDGF) and transforming growth factor beta (TGF-beta). Following hemostasis, the neutrophils then enter the wound site and begin the critical task of phagocytosis to remove foreign materials, bacteria and damaged tissue. As part of this inflammatory phase, the macrophages appear and continue the process of phagocytosis as well as releasing more PDGF and TGF beta. Once the wound site is cleaned out, fibroblasts migrate in to begin the proliferative phase and deposit new extracellular matrix. The new collagen matrix then becomes cross-linked and organized during the final remodeling phase. In order for this efficient and highly controlled repair process to take place, there are numerous cell-signaling events that are required. In pathologic conditions such as non-healing pressure ulcers, this efficient and orderly process is lost and the ulcers are locked into a state of chronic inflammation characterized by abundant neutrophil infiltration with associated reactive oxygen species and destructive enzymes. Healing proceeds only after the inflammation is controlled. On the opposite end of the spectrum, fibrosis is characterized by excessive matrix deposition and reduced remodeling. Often fibrotic lesions are associated with increased densities of mast cells. By understanding the functional relationships of these biological processes of normal compared to abnormal wound healing, hopefully new strategies can be designed to treat the pathological conditions.