Co-administration of Ketamine in Pediatric Patients with Neurologic Conditions at Risk for Intracranial Hypertension.

BACKGROUND: Ketamine has traditionally been avoided as an induction agent for tracheal intubation in patients with neurologic conditions at risk for intracranial hypertension due to conflicting data in the literature. The objective of this study was to evaluate and compare the effects of ketamine versus other medications as the primary induction agent on peri-intubation neurologic, hemodynamic and respiratory associated events in pediatric patients with neurologic conditions at risk for intracranial hypertension. METHODS: This retrospective observational study enrolled patients < 18 years of age at risk for intracranial hypertension who were admitted to a quaternary children's hospital between 2015 and 2020. Associated events included neurologic, hemodynamic and respiratory outcomes comparing primary induction agents of ketamine versus non-ketamine for tracheal intubation. RESULTS: Of 143 children, 70 received ketamine as the primary induction agent prior to tracheal intubation. Subsequently after tracheal intubation, all the patients received adjunct analgesic and sedative medications (fentanyl, midazolam, and/or propofol) at doses that were inadequate to induce general anesthesia but would keep them comfortable for further diagnostic workup. There were no significant differences between associated neurologic events in the ketamine versus non-ketamine groups (p = 0.42). This included obtaining an emergent computed tomography scan (p = 0.28), an emergent trip to the operating room within 5 h of tracheal intubation (p = 0.6), and the need for hypertonic saline administration within 15 min of induction drug administration for tracheal intubation (p = 0.51). There were two patients who had clinical and imaging evidence of herniation, which was not more adversely affected by ketamine compared with other medications (p = 0.49). Of the 143 patients, 23 had pre-intubation and post-intubation intracranial pressure values recorded; 11 received ketamine, and 3 of these patients had intracranial hypertension that resolved or improved, whereas the remaining 8 children had intracranial pressure within the normal range that was not exacerbated by ketamine. There were no significant differences in overall associated hemodynamic or respiratory events during tracheal intubation and no 24-h mortality in either group. CONCLUSIONS: The administration of ketamine as the primary induction agent prior to tracheal intubation in combination with other agents after tracheal intubation in children at risk for intracranial hypertension was not associated with an increased risk of peri-intubation associated neurologic, hemodynamic or respiratory events compared with those who received other induction agents.

Comparison of alfaxalone and propofol on haematological and serum biochemical variables in cats undergoing radiotherapy with sevoflurane maintenance.

OBJECTIVE: To evaluate effects of repeated alfaxalone or propofol administration on haematological and serum biochemical variables in cats undergoing radiotherapy. STUDY DESIGN: Prospective, block-randomized, clinical trial. ANIMALS: A group of 39 client-owned cats. METHODS: After butorphanol (0.2 mg kg-1) and midazolam (0.1 mg kg-1) sedation, cats were randomly assigned to receive either alfaxalone or propofol for induction of anaesthesia and sevoflurane maintenance. Cats were anaesthetized daily with the same induction agent for 10-12 days. Complete blood counts, reticulocytes, Heinz body score and serum biochemistry were performed before the first treatment (T1), at T6, T10 and 3 weeks after the final treatment (T21). Cumulative induction agent dose for each cat at each time point was evaluated for an effect on Heinz body score. Data are shown as mean ± standard deviation; p < 0.05. RESULTS: At baseline there were no significant differences in signalment or blood variables between groups. A significant decrease in haematocrit of 2.3% ± 0.77 (p = 0.02) between T1-T6 and T1-T10 [mean 4.1% (± 0.78, p < 0.0001)] was detected, with a significant increase in haematocrit of 2.1% ± 0.80 (p = 0.046) between T6-T21 and 4.0% ± 0.8 (p < 0.001) between T10-T21. Heinz body score significantly increased by 1.86 ± 0.616 (p = 0.013) between T1-T10. In the propofol group, reticulocytes increased significantly between T1-T6 [mean 23,090 µL-1 ± 7670 (p = 0.02)] and T1-T10 [mean 27,440 µL-1 ± 7990 (p = 0.007)]. Mean cumulative dose at T10 was 19.65 mg kg-1 ± 5.3 and 43.4 mg kg-1 ± 14.4 for alfaxalone and propofol, respectively, with no significant effect on Heinz body formation at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Haematocrit decreased in both groups with recovery after 3 weeks. Repeated alfaxalone and propofol administration was not associated with marked haematological or serum biochemistry changes.

Development of CMV-specific cytotoxic T cells (CMV-Tc) in pediatric renal transplant recipients with CMV viremia.

BACKGROUND: Viral infections are controlled primarily by viral-specific T cells, raising concern for adequate T-cell response to clear CMV infection in transplant recipients receiving lymphocyte-depleting agents (LDA). We examined the rates of CMV viremia and clearance, seroconversion, and CMV-specific CD8+ T cell (CMV-Tc) activity with class of induction agent received. METHODS: Retrospective review of 45 pediatric renal transplant recipients who received induction with LDA (n = 31) or non-LDA (NLDA; n = 14) received valganciclovir prophylaxis for 6 months post-transplant and CMV-PCR monitoring. CMV-Tc was measured by intracellular IFNγ flow cytometry, when possible, at baseline, 1 month after CMV viremia (>5 copies/PCR) and serially until CMV-Tc was positive (≥0.2%). RESULTS: Viremia rates at 1, 2, and 4 years post-transplant were higher in LDA vs. NLDA (46.3% vs. 7.2%, 64.2% vs. 7.2%, and 64.2% vs. 7.2%, respectively; p = .002). Viremia rates at these time points in seronegative LDA (50.3%, 71.6%, 71.6%) were significantly or near significantly higher than seronegative NLDA (9.1%, 9.1%, 9.1%; p = .004), seropositive-LDA (22.3%, 22.3%, 22.3%; p = .07), or seropositive NLDA (0%, 0%, 0%; p = .07). Eleven of 17 (64.7%) viremic subjects required valganciclovir dose reduction during the prophylaxis period for leukopenia. All viremic LDA patients developed CMV-Tc. One viremic NLDA patient did not develop CMV-Tc. No patients developed CMV disease. CONCLUSION: CMV seronegative pediatric renal transplant patients receiving LDA are more likely to have valganciclovir prophylaxis dose reduction and develop subclinical CMV viremia; however, all developed CMV-Tc. Larger prospective studies are needed to further understand the effects of induction agents on CMV-Tc and CMV-Tc's role post-transplant.

The Effect of Propofol on Peri-Induction Hemodynamics and Resuscitation in Operative Penetrating Trauma.

BACKGROUND: Hemorrhaging trauma patients may be disproportionately affected by choice of induction agent during rapid sequence intubation (RSI). Etomidate, ketamine, and propofol are safe in the trauma population-at-large but have not been assessed in patients with ongoing hemorrhage. We hypothesize that in hemorrhaging patients with penetrating injury, propofol deleteriously affects peri-induction hypotension compared to etomidate and ketamine. METHODS: Retrospective cohort study. Primary outcome was the effect of induction agent on peri-induction systolic blood pressure. Secondary outcomes were the incidence of peri-induction vasopressor use and quantity of peri-induction blood transfusion requirements. Linear multivariate regression modeling assessed the effect of induction agent on the variables of interest. RESULTS: 169 patients were included, 146 received propofol and 23 received etomidate or ketamine. Univariate analysis revealed no difference in peri-induction systolic blood pressure (P = .53), peri-induction vasopressor administration (P = .62), or transfusion requirements within the first hour after induction (PRBC P = .24, FFP P = .19, PLT P = .29). Choice of RSI agent did not independently predict peri-induction systolic blood pressure or blood product administration. Rather, only presenting shock index independently predicted peri-induction hypotension. CONCLUSIONS: This is the first study to directly assess the peri-induction effects of anesthetic induction agent choice in penetrating trauma patients undergoing emergent hemorrhage control surgery. Propofol does not appear to worsen peri-induction hypotension regardless of dose. Patient physiology is most predictive of peri-induction hypotension.

Necessity of induction agent modification for old age kidney transplant recipients.

Background: Immunosenescence gradually deteriorates the function of the immune system, making elderly patients susceptible to infection, while reducing rejection of organ transplants. Therefore, age-adaptive immunosuppression is necessary in the elderly. We evaluated clinical outcomes such as rejection and infection rate when using basiliximab and rabbit anti-thymocyte globulin (r-ATG) as induction agents in elderly and young organ transplant recipients. Methods: We retrospectively reviewed patients who underwent kidney transplantation (KT) between June 2011 and April 2019. We enrolled 704 adult KT patients and classified the patients into groups according to patient age. We compared the outcomes of infection and biopsy-proven acute rejection (BPAR) according to the type of induction agent (basiliximab and r-ATG [4.5 mg/kg]). Results: The patient group included 520 recipients (74.6%) in the younger recipient group and 179 recipients (25.4%) in the older recipient group. When r-ATG was used as an induction agent, BPAR within 6 months occurred less (p = 0.03); however, infections within 6 months were higher in older recipients. Deaths due to infection were more common in older recipients (p = 0.003). Conclusion: It may be necessary to use less intensive induction therapy for older recipients, of which dose reduction of r-ATG is one option.

A Nomogram Model for Post-Intubation Hypotension in Patients with Severe Pneumonia in the Emergency Department.

Background: Post-intubation hypotension (PIH) frequently occurs in the management of critically ill patients and is associated with prognosis. The study aimed to construct a prediction model for PIH events by analyzing risk factors in patients with severe pneumonia in the emergency department. Methods: We retrospectively enrolled 572 patients with severe pneumonia diagnosed in the emergency department of West China Hospital of Sichuan University. Five hundred patients with severe pneumonia who underwent endotracheal intubation were included in the study. All patients were randomized according to 7:3 and divided into a training cohort (n=351) and a validation cohort (n=149). Risk factors for PIH were analyzed using Least Absolute Shrinkage and Selection Operator (LASSO) and multivariable logistic regression. Calibration curves, receiver operating characteristic (ROC) curve, and decision curve analysis were applied to assess the predictive model's fitness, discrimination, and clinical utility. Results: A total of 500 patients with severe pneumonia who underwent endotracheal intubation were enrolled in this study, and PIH occurred in 234 (46.8%) of these patients. Age, heart rate, systolic blood pressure, chronic obstructive pulmonary disease, acute physiology and chronic health evaluation II score, and induction agent use were identified as significant risk factors for the occurrence of PIH. Additionally, the body mass index was the opposite of the above. The area under the ROC curve (AUC) for the model was 0.856 (95% CI, 0.818-0.894) in the training cohort and 0.849 (95% CI, 0.788-0.910) in the validation cohort. The nomogram model was validated and demonstrated good calibration and high net clinical benefit. Finally, to facilitate application by clinicians, an online server has been set up which can be accessed free of charge via the website https://chinahospitals.shinyapps.io/DynNomapp/. Conclusion: The nomogram is used for individualized prediction of patients with severe pneumonia prior to intubation and is simple to perform with high clinical value.

Mapping haemodynamic changes with rapid sequence induction agents in the emergency department.

OBJECTIVE: Patients intubated in the ED are at an increased risk of post-intubation hypotension. However, evidence regarding the most appropriate induction agent is lacking. The present study aims to describe and compare the haemodynamic effect of propofol, ketamine and thiopentone during rapid sequence induction. METHODS: This is an observational study using data prospectively collected from the Australian and New Zealand Emergency Department Airway Registry between June 2012 and March 2019. The distribution of induction agents across medical and trauma patients were obtained with descriptive statistics. The relationship between induction agent, dose and change in pre- and post-intubation systolic blood pressure (SBP) was described using multivariable logistic regression. The SBP pre- and post-intubation was the primary measure of haemodynamic stability. RESULTS: From the 5063 intubation episodes, 2229 met the inclusion criteria. Of those, 785 (35.2%) patients were induced with thiopentone, 773 (34.7%) with propofol and 671 (30.1%) with ketamine. Of the included population, 396 (17.8%) patients experienced a reduction in pre-intubation SBP exceeding 20%. Both propofol (P = 0.01) and ketamine (P = 0.01) had an independent and dose-dependent association with hypotension, noting that a higher proportion of patients induced with ketamine had a shock index exceeding 0.9. CONCLUSION: Propofol was associated with post-intubation hypotension and it is recommended clinicians consider using the lowest effective dose to reduce this risk. Reflecting its perceived haemodynamic stability, patients who received ketamine were more likely to have a higher shock index; however, there was also an association with post-intubation hypotension.

Intravenous Propofol Allows Fast Intubation in Neonates and Young Infants Undergoing Major Surgery.

Aim of the study: In selected surgical neonates and infants, the rapidity of induction and intubation may represent an important factor for their safety. Propofol is an anesthetic characterized by a rapid onset and fast recovery time that may reduce time of anesthetic induction and improve post-anesthetic outcome. The aim of this study was to evaluate the safety and efficacy of anesthesia induction in full-term neonates and young infants after propofol bolus administration. Methods: A retrospective case-control study including infants below 6 months of age, undergoing general anesthesia between 2011 and 2013, was carried out. Patients that received intravenous propofol bolus to induce anesthesia were compared to patients who received inhaled sevoflurane. Time to reach successful orotracheal intubation (OTI) was measured in seconds. The quality of OTI was defined as "excellent," "good," and "poor," based on established classification and was reported. Hemodynamic parameters as systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), heart rate (HR), and oxygen saturation (SaO2) were collected before OTI (t0), at OTI (t1), and at spontaneous breathing recovery (t2). Main adverse effects were recorded for both groups. Results are median (IQ range) or prevalence; p < 0.05 was considered significant. Results: 160 infants were enrolled in the study, 80 received propofol and 80 inhaled sevoflurane. Major surgery (involving organs in the thoracic, abdominal, or pelvic cavities) was performed in 64 and 54% of patients in the propofol and sevoflurane group, respectively (p = 0.07). Patients in the propofol group showed a shorter time for OTI [11.5 (4.0-65) vs. 360.0 (228.0-720.0) seconds, (p < 0.0001)]. No difference was found in the quality of OTI between the two groups. No significant complications were recorded in either group. Conclusions: Propofol is a safe and effective anesthetic in neonates and infants permitting rapid induction of anesthesia and rapid intubation, without negative impact on the quality of intubation and haemodynamic compromise.

New and developing anesthesia drugs.

INTRODUCTION: In recent years, new anesthetic drugs with potentially better pharmacokinetic and pharmacodynamic properties are under development with good progress. Some of the most promising drugs are reviewed in this article. Areas covered: A literature review was performed using Ovid and Medline as the search engine. Articles published from January 2000 to December 2016 were included for review. Efforts have been made to eliminate duplicated studies. Expert opinion: This is an up-to-date review on new and developing anesthesia drugs. It will give readers information on the pharmacology and clinical significance of these new drugs.

Impact of steroid maintenance on the outcomes in first-time deceased donor kidney transplant recipients: Analysis by induction type.

AIM: To analyze the impact of steroid maintenance on the outcomes in kidney transplant recipients stratified by induction agent received. METHODS: Patients who underwent first-time deceased donor kidney transplantation between 2000 and 2008 after receiving induction therapy with rabbit-antithymocyte globulin (r-ATG), alemtuzumab or an interleukin-2 receptor blocker (IL-2B) and discharged on a calcineurin inhibitor (CNI)/mycophenolate mofetil (MMF)-regimen along with or without steroids were identified from the Organ Procurement and Transplant Network/United Network of Organ Sharing database. For each induction type, adjusted overall and death-censored graft as well as patient survivals were compared between patients discharged on steroid vs no steroid. Among r-ATG induced patients, analysis was repeated after splitting the group into low and high immune risk groups. RESULTS: Among the 37217 patients included in the analysis, 17863 received r-ATG (steroid = 13001, no-steroid = 4862), 3028 alemtuzumab (steroid = 852, no-steroid = 2176) and 16326 IL-2B (steroid = 15008, no-steroid = 1318). Adjusted overall graft survival was inferior (HR = 1.16, 95%CI: 1.06-1.27, P = 0.002) with similar death-censored graft survival (HR = 0.99, 95%CI: 0.86-1.14, P = 0.86) for steroid vs no-steroid groups in r-ATG induced patients. Both adjusted overall and death-censored graft survivals for steroid vs no-steroid groups were similar in alemtuzumab (HR = 0.92, 95%CI: 0.73-1.15, P = 0.47 and HR = 0.87, 95%CI: 0.62-1.22, P = 0.43 respectively) and IL-2B (HR = 1.05, 95%CI: 0.91-1.21, P = 0.48 and HR = 0.94, 95%CI: 0.75-1.18, P = 0.60 respectively) induced groups. Adjusted patient survivals were inferior for steroid vs no-steroid groups in r-ATG induced (HR = 1.31, 95%CI: 1.15-1.49, P < 0.001) but similar in alemtuzumab (HR = 1.02, 95%CI: 0.75-1.38, P = 0.92) and IL-2B (HR = 1.17, 95%CI: 0.97-1.40, P = 0.10) induced patients. Among the r-ATG induced group there were 4346 patients in the low immune risk and 13517 patients in the high immune risk group. Adjusted overall graft survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.34, 95%CI: 1.09-1.64, P = 0.001) and high immune (HR = 1.18, 95%CI: 1.07-1.30, P = 0.005) risk groups. Adjusted death-censored graft survivals for steroid vs no steroid groups were similar in both low (HR = 1.06, 95%CI: 0.78-1.45, P = 0.70) and high (HR = 1.04, 95%CI: 0.98-1.20, P = 0.60) immune risk groups. Adjusted patient survivals were inferior for steroid vs no steroid groups in both low immune (HR = 1.54, 95%CI: 1.18-2.02, P < 0.001) and high immune (HR = 1.32, 95%CI: 1.16-1.51, P = 0.002) risk groups. Overall, there were significantly higher deaths from infections and cardiovascular causes in patients maintained on steroids. CONCLUSION: Our study showed an association between steroid addition to a CNI/MMF-maintenance regimen and increased death with functioning graft in patients receiving r-ATG induction for first-time deceased donor kidney transplantation.