Effects of continuous ketamine infusion on hemodynamics and mortality in critically ill children.
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ABSTRACT:
SUBMITTER: Park S
PROVIDER: S-EPMC6799949 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Hyperglycemia is associated with increased morbidity and mortality in critically ill patients and strict glycemic control has become standard care for adults. Recent studies have questioned the optimal targets for such management and reported increased rates of iatrogenic hypoglycemia in both critically ill children and adults. The ability to provide accurate, real-time continuous glucose monitoring would improve the efficacy and safety of this practice in critically ill patients. The aim of our study is to determine if a continuous, interstitial glucose monitor will correlate with blood glucose values in critically ill children.We evaluated 50 critically ill children age 6 weeks to 16 years old with a commercially available continuous glucose monitor (CGM; Medtronic Guardian®). CGM values and standard blood glucose (BG) values were compared. During the study, no changes in patient management were made based on CGM readings alone.Forty-seven patients had analyzable CGM data. A total of 1,555 CGM and routine BG measurements were compared using Clarke error grid and Bland-Altman analysis. For all readings, 97.9% were within clinically acceptable agreement. The mean absolute relative difference between CGM and BG readings was 15.3%. For the 1,555 paired CGM and BG measurements, there is a statistically significant linear relationship between CGM values and BG (P < .0001). A high degree of clinical agreement existed in three subpopulation analyses based on age, illness severity, and support measures. This included some of our smallest patients (that is, < 12 months old), those who required vasopressors, and those who were treated for critical illness hyperglycemia.In one of the largest studies to date, in a highly vulnerable ICU population, CGM values have a clinically acceptable correlation with the BG values now used diagnostically and therapeutically. Our data contest the theoretical concerns posed by some regarding CGM use in the ICU. The existing medical evidence may now support a role for CGM devices in the identification and management of hyperglycemia in diverse ICU settings.
| S-EPMC3219278 | biostudies-other
Project description:Attainment of appropriate pharmacokinetic-pharmacodynamic (PK-PD) targets for antimicrobial treatment is challenging in critically ill patients, particularly for cefepime, which exhibits a relative narrow therapeutic-toxic window compared to other beta-lactam antibiotics. Target-controlled infusion (TCI) systems, which deliver drugs to achieve specific target drug concentrations, have successfully been implemented for improved dosing of sedatives and analgesics in anesthesia. We conducted a clinical trial in an intensive care unit (ICU) to investigate the performance of TCI for adequate target attainment of cefepime. Twenty-one patients treated with cefepime according to the standard of care were included. Cefepime was administered through continuous infusion using TCI for a median duration of 4.5?days. TCI was based on a previously developed population PK model incorporating the estimated creatinine clearance based on the Cockcroft-Gault formula as the input variable to calculate cefepime clearance. A cefepime blood concentration of 16?mg/liter was targeted. To evaluate the measured versus predicted plasma concentrations, blood samples were taken (median of 10 samples per patient), and total cefepime concentrations were measured using ultraperformance liquid chromatography-tandem mass spectrometry. The performance of the TCI system was evaluated using Varvel criteria. Half (50.3%) of the measured cefepime concentrations were within ±30% around the target value of 16?mg liter-1 The wobble was 11.4%, the median performance error (MdPE) was 21.1%, the median absolute performance error (MdAPE) was 32.0%, and the divergence was -3.72% h-1 Based on these results, we conclude that TCI is useful for dose optimization of cefepime in ICU patients. (This study has been registered at ClinicalTrials.gov under identifier NCT02688582.).
| S-EPMC7187597 | biostudies-literature
Project description:Severe sepsis (SS) in pediatric oncology patients is a leading cause of morbidity and mortality. We investigated the incidence of and risk factors for morbidity and mortality among children diagnosed with cancer from 2008 to 2012, and admitted with SS during the 3 years following cancer diagnosis. A total of 1,002 children with cancer were included, 8% of whom required pediatric intensive care unit (PICU) admission with SS. Death and/or multiple organ dysfunction syndrome occurred in 34 out of 99 PICU encounters (34%). Lactate level and history of stem-cell transplantation were significantly associated with the development of death and/or organ dysfunction ( p ?<?0.05).
| S-EPMC6687451 | biostudies-literature
Project description:Alfaxalone is an injectable anesthetic agent that is used in veterinary medicine for general anesthesia. We evaluated the safety and efficacy of alfaxalone delivered through continuous rate infusion by comparing ketamine-xylazine-alfaxalone (KXA) anesthesia with ketamine-xylazine (KX) anesthesia in Sprague-Dawley rats. Anesthesia was induced in male and female rats by using subcutaneous KX. After induction, rats in the KXA group received alfaxalone (10 mg/kg/h IV) for 35 min, whereas rats in the KX group did not receive alfaxalone. At the end of the trial, alfaxalone was discontinued, and xylazine was reversed in all rats by using atipamezole. Throughout anesthesia, we assessed forepaw withdrawal reflex (FPWR), hindpaw withdrawal reflex (HPWR), response to surgical stimulation, heart rate, respiratory rate, SpO?, body temperature, and time to standing. KXA produced a reliable surgical plane of anesthesia, as evidenced by the loss of both FPWR and HPWR and lack of response to surgical stimulation in all 16 rats, whereas only 6 of the 16 rats in the KX group lost HPWR. No rat in the KXA group regained a paw withdrawal reflex during alfaxalone administration, whereas 3 of the 12 rats (25%) in the KX group that reached a surgical plane of anesthesia exited that plane within the 35-min timeframe. Neither heart rate, respiratory rate, SpO?, body temperature, nor time to standing differed between KXA and KX groups; and there were no sex-associated differences in anesthesia response. These results indicate that alfaxalone (10 mg/kg/h IV) delivered through continuous rate infusion, in combination with ketamine and xylazine, provides a safe, prolonged, and reliable surgical plane of anesthesia in rats.
| S-EPMC7073396 | biostudies-literature
Project description:BACKGROUND:Optimal antimicrobial drug exposure in the lung is required for successful treatment outcomes for nosocomial pneumonia. Little is known about the intrapulmonary pharmacokinetics (PK) of meropenem when administered by continuous infusion (CI). The aim of this study was to evaluate the PK of two dosages of meropenem (3 g vs 6 g/day by CI) in the plasma and epithelial lining fluid (ELF) in critically ill patients with nosocomial pneumonia. METHODS:Thirty-one patients (81% male, median (IQR) age 72 (22) years) were enrolled in a prospective, randomized, clinical trial. Sixteen patients received 1 g/8 h and 15 2 g/8 h by CI (8 h infusion). Plasma and ELF meropenem concentrations were modeled using a population methodology, and Monte Carlo simulations were performed to estimate the probability of attaining (PTA) a free ELF concentration of 50% of time above MIC (50% fT>MIC), which results in logarithmic killing and the suppression of resistance in experimental models of pneumonia. RESULTS:The median (IQR) of meropenem AUC0-24 h in the plasma and ELF was 287.6 (190.2) and 84.1 (78.8) mg h/L in the 1 g/8 h group vs 448.1 (231.8) and 163.0 (201.8) mg h/L in the 2 g/8 h group, respectively. The penetration ratio was approximately 30% and was comparable between the dosage groups. In the Monte Carlo simulations, only the highest approved dose of meropenem of 2 g/8 h by CI allowed to achieve an optimal PTA for all isolates with a MIC < 4 mg/L. CONCLUSIONS:An increase in the dose of meropenem administered by CI achieved a higher exposure in the plasma and ELF. The use of the highest licensed dose of 6 g/day may be necessary to achieve an optimal coverage in ELF for all susceptible isolates (MIC ≤ 2 mg/L) in patients with conserved renal function. An alternative therapy should be considered when the presence of microorganisms with a MIC greater than 2 mg/L is suspected. TRIAL REGISTRATION:The trial was registered in the European Union Drug Regulating Authorities Clinical Trials Database (EudraCT-no. 2016-002796-10). Registered on 27 December 2016.
| S-EPMC7026992 | biostudies-literature
Project description:BackgroundIn critically ill children, detection of intra-abdominal hypertension (IAH > 10 mmHg) and abdominal compartment syndrome (ACS = IAH + organ dysfunction) is paramount and usually monitored through intra-vesical pressures (IVP) as current standard. IVP, however, carries important disadvantages, being time-consuming, discontinuous, with infection risk through observer-dependent manipulation, and ill-defined for catheter sizes. Therefore, we sought to validate air-capsule-based measurement of intra-gastric pressure (ACM-IGP).MethodsWe prospectively compared ACM-IGP with IVP both in vivo and in vitro (water column), according to Abdominal-Compartment-Society validation criteria. We controlled for patient age, admission diagnosis, gastric filling/propulsive medication, respiratory status, sedation levels and transurethral catheters, all influencing intra-abdominal pressure (IAP).ResultsIn tertiary care PICU setting, finally, n = 97 children were enrolled (median age, 1.3 years [range 0 days-17 years], LOS-PICU 8.0 [1-332] days, PRISM-III-Score 13 [0-35]). In n = 2.770 measurements pairs, median IAP was 6.7 [0.9-23.0] mmHg, n = 38 (39%) children suffered from IAH > 10 mmHg, n = 4 from ACS. In vitro against water column, ACM-IGP correlated perfectly (r2 0.99, mean bias - 0.1 ± 0.5 mmHg, limits of agreement (LOA) - 1.1/+ 0.9, percentage error [PE] 12%) as compared with IVP (r2 0.98, bias + 0.7 ± 0.6 mmHg, LOA - 0.5/+ 1.9, PE 15%). With larger IVP catheters at higher pressure levels, IVP underestimated pressures against water column. In vivo, agreement between either technique was strong (r2 0.95, bias 0.3 ± 0.8 mmHg, LOA - 1.3/+ 1.9 mmHg, PE 23%). No impact of predefined control variables on measurement agreement was observed.ConclusionsIn a large PICU population with high IAH prevalence, ACM-IGP agreed favourably with IVP. More widespread usage of ACM-IGP may improve detection rates of ACS in critically ill children. Trial registration WHO-ICTRP-No. DRKS00006556 (German Clinical Trial Register). Registered 12th September 2014, URL: https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00006556.
| S-EPMC8141480 | biostudies-literature
Project description:ObjectivesDeveloping effective therapies to reduce morbidity and mortality requires knowing the responsible pathophysiologies and the therapeutic advances that are likely to be impactful. Our objective was to determine at the individual patient level the important pathophysiological processes and needed therapeutic additions and advances that could prevent or ameliorate morbidities and mortalities.DesignStructured chart review by pediatric intensivists of PICU children discharged with significant new morbidity or mortality to determine the pathophysiologies responsible for poor outcomes and needed therapeutic advances.SettingMulticenter study (eight sites) from the Collaborative Pediatric Critical Care Research Network of general and cardiac PICUs.PatientsFirst PICU admission of patients from December 2011 to April 2013.InterventionsNone.Measurements and main resultsTwo-hundred ninety-two patients were randomly selected from 681 patients discharged with significant new morbidity or mortality. The median age was 2.4 years, 233 (79.8%) were in medical/surgical ICUs, 59 (20.2%) were in cardiac ICUs. Sixty-five (22.3%) were surgical admissions. The outcomes included 117 deaths and 175 significant new morbidities. The most common pathophysiologies contributing to the poor outcomes were impaired substrate delivery (n = 158, 54.1%) and inflammation (n = 104, 35.6%). There were no strong correlations between the pathophysiologies and no remarkable clusters among them. The most common therapeutic needs involved new drugs (n = 149, 51.0%), cell regeneration (n = 115, 39.4%), and immune and inflammatory modulation (n = 79, 27.1%). As with the pathophysiologies, there was a lack of strong correlations or meaningful clusters in the suggested therapeutic needs.ConclusionsThere was no single dominant pathophysiology or cluster of pathophysiologies responsible for poor pediatric critical care outcomes. Therapeutic needs often involved therapies that are not close to implementation such as cell regeneration, improved organ transplant, improved extracorporeal support and artificial organs, and improved drugs.
| S-EPMC7242139 | biostudies-literature
Project description:BackgroundThe rapid development in big data analytics and the data-rich environment of intensive care units together provide unprecedented opportunities for medical breakthroughs in the field of critical care. We developed and validated a machine learning-based model, the Pediatric Risk of Mortality Prediction Tool (PROMPT), for real-time prediction of all-cause mortality in pediatric intensive care units.MethodsUtilizing two separate retrospective observational cohorts, we conducted model development and validation using a machine learning algorithm with a convolutional neural network. The development cohort comprised 1445 pediatric patients with 1977 medical encounters admitted to intensive care units from January 2011 to December 2017 at Severance Hospital (Seoul, Korea). The validation cohort included 278 patients with 364 medical encounters admitted to the pediatric intensive care unit from January 2016 to November 2017 at Samsung Medical Center.ResultsUsing seven vital signs, along with patient age and body weight on intensive care unit admission, PROMPT achieved an area under the receiver operating characteristic curve in the range of 0.89-0.97 for mortality prediction 6 to 60 h prior to death. Our results demonstrated that PROMPT provided high sensitivity with specificity and outperformed the conventional severity scoring system, the Pediatric Index of Mortality, in predictive ability. Model performance was indistinguishable between the development and validation cohorts.ConclusionsPROMPT is a deep model-based, data-driven early warning score tool that can predict mortality in critically ill children and may be useful for the timely identification of deteriorating patients.
| S-EPMC6694497 | biostudies-literature
Project description: Not available
| S-EPMC6517095 | biostudies-literature
Project description:BackgroundChildren in PICUs experience negative sequelae of immobility; however, interprofessional staff concerns about safety are a barrier to early mobilization. Our objective was to determine the safety profile of early mobilization in PICU patients.MethodsWe conducted a secondary analysis of a 2-day study focused on physical rehabilitation in 82 PICUs in 65 US hospitals. Patients who had ≥72-hour admissions and participated in a mobility event were included. The primary outcome was occurrence of a potential safety event during mobilizations.ResultsOn 1433 patient days, 4658 mobility events occurred with a potential safety event rate of 4% (95% confidence interval [CI], 3.6%-4.7%). Most potential safety events were transient physiologic changes. Medical equipment dislodgement was rare (0.3%), with no falls or cardiac arrests. Potential safety event rates did not differ by patient age or sex. Patients had higher potential safety event rates if they screened positive for delirium (7.8%; adjusted odds ratio, 5.86; 95% CI, 2.17-15.86) or were not screened for delirium (4.7%; adjusted odds ratio, 3.98; 95% CI, 1.82-8.72). There were no differences in potential safety event rates by PICU intervention, including respiratory support or vasoactive support.ConclusionsEarly PICU mobilization has a strong safety profile and medical equipment dislodgement is rare. No PICU interventions were associated with increased potential safety event rates. Delirium is associated with higher potential safety event rates. These findings highlight the need to improve provider education and confidence in mobilizing critically ill children.
| S-EPMC9648104 | biostudies-literature