Bolus Infusion Research Articles

Steady-State Piperacillin Concentrations in the Proximity of an Orthopedic Implant: A Microdialysis Porcine Study

Implant-associated osteomyelitis is one of the most feared complications following orthopedic surgery. Although the risk is low, sufficient antibiotic protection of the implant surface is important. The aim of this study was to assess steady-state piperacillin concentrations in the proximity of an orthopedic implant. Time above the minimal inhibitory concentration (fT>MIC) was evaluated for MIC of 8 (low target) and 16 μg/mL (high target). Six female pigs received an intravenous bolus infusion of 4 g/0.5 g piperacillin/tazobactam over 30 min every 6 h. Steady state was assumed achieved in the third dosing interval (12-18 h). Microdialysis catheters were placed in a cannulated screw in the proximal tibial cancellous bone, in cancellous bone next to the screw, and in cancellous bone on the contralateral tibia. Dialysates were collected from time 12 to 18 h and plasma samples were collected as reference. For the low piperacillin target (8 µg/mL), comparable mean fT>MIC across all the investigated compartments (mean range: 54-74%) was found. For the high target (16 µg/mL), fT>MIC was shorter inside the cannulated screw (mean: 16%) than in the cancellous bone next to the screw and plasma (mean range: 49-54%), and similar between the two cancellous bone compartments. To reach more aggressive piperacillin fT>MIC targets in relation to the implant, alternative dosing regimens such as continuous infusion may be considered.

A 5-Minute Delay From Bolus Injection to Infusion Halves Plasma Concentration of Tissue Plasminogen Activator

BackgroundReducing the time between onset of cerebral infarction and treatment with tissue plasminogen activator improves the prognosis of patients with cerebral infarction. Diverse dosing protocols have been developed with the aim of reducing the time to bolus injection; however, only a few studies have investigated the methods and effects of the interrupted time between bolus and post-bolus infusion. ObjectiveWe evaluated the impact of the interrupted time on pharmacokinetic parameters. MethodsWe calculated the changes in alteplase concentration after a bolus injection with high precision, in relation to different interval times. Simulations were performed using the linpk package of the statistical analysis software R. Post-bolus infusion was initiated at 0-, 5-, 15-, and 30-min intervals after bolus dosing. The calculation interval was set as 6 s. ResultsAlteplase concentration rose to 1.23 mg/mL after bolus dosing. However, it dropped to 0.53 mg/mL (43.4%) during a 5-min interval, 0.27 mg/mL (22.23%) during a 15-min interval, and 0.10 mg/mL (8.38%) during a 30-min interval. ConclusionsBecause of the short half-life of alteplase, even a short delay in initiating post-bolus infusion can cause a significant reduction in serum alteplase concentration.

Hemodynamic responses to 1 MAC desflurane inhalation during anesthesia induction with propofol bolus and remifentanil continuous infusion: a prospective randomized single-blind clinical investigation

BackgroundDesflurane is not recommended during anesthesia induction because of its sympathetic stimulation effect, particularly in patients with myocardial ischemic disease. To date, the hemodynamic response to 1 MAC desflurane inhalation in combination with remifentanil infusion during anesthesia induction has rarely been reported.MethodsThis investigation was designed to compare hemodynamic responses to 1 MAC desflurane (group D, n = 200) with sevoflurane (group S, n = 200) during anesthesia induction and endotracheal intubation in adult patients undergoing elective spine surgery. Subgroup analysis of the different age subgroups was also performed. With continuous infusion of remifentanil 0.1 μg/kg/min, anesthesia was induced with propofol bolus, and endotracheal intubation was performed after muscle relaxation. Heart rate (HR) and mean arterial blood pressure (MAP) were measured every minute for 5 min after anesthesia induction (T1-5) and after endotracheal intubation (T6-10).ResultsHR was significantly higher in group D (n = 182) than in group S (n = 173) at T3-10 except at T6 (1 min after intubation) (all P < 0.05). In the age-based subgroup analyses, which subdivided the group D and S into four subgroups based on patient’s age, the changes in HR from baseline values were significantly different between the coeval subgroups of patients in their 20–29 years and 30–39 years of age (all P < 0.05). MAP was reduced from baseline value, irrespective of group and age.ConclusionInhalation of 1 MAC desflurane during anesthesia induction with propofol bolus and remifentanil continuous infusion and during endotracheal intubation was more likely to induce elevations in HR more likely than 1 MAC sevoflurane, especially in younger patients.Trial registrationThis study was registered in the Clinical Research Information Service (CRIS, http://cris.nih.go.kr) of the Republic of Korea on Feb 12, 2016 (Registration No. KCT 0,001,813).

Impact of framing scheme optimization and smoking status on binding potential analysis in dynamic PET with [11C]ABP688

BackgroundFor positron emission tomography (PET) ligands, such as [11C]ABP688, to be able to provide more evidence about the glutamatergic hypothesis in schizophrenia (SZ), quantification bias during dynamic PET studies and its propagation into the estimated values of non-displaceable binding potential (BPND) must be addressed. This would enable more accurate quantification during bolus + infusion (BI) neuroreceptor studies and further our understanding of neurological diseases. Previous studies have shown BPND-related biases can often occur due to overestimated cerebellum activity (reference region). This work investigates whether an alternative framing scheme can minimize quantification biases propagated into BPND, whether confounders, such as smoking status, need to be controlled for during the study, and what the consequences for the data interpretation following analysis are. A group of healthy controls (HC) and a group of SZ patients (balanced and unbalanced number of smokers) were investigated with [11C]ABP688 and a BI protocol. Possible differences in BPND quantification as a function of smoking status were tested with constant 5 min (‘Const 5 min’) and constant true counts (‘Const Trues’) framing schemes. In order to find biomarkers for SZ, the differences in smoking effects were compared between groups. The normalized BPND and the balanced number of smokers and non-smokers for both framing schemes were evaluated.ResultsWhen applying F-tests to the ‘Const 5 min’ framing scheme, effect sizes (η2p) and brain regions which showed significant effects fluctuated considerably with F = 50.106 ± 54.948 (9.389 to 112.607), P-values 0.005 to < 0.001 and η2p = 0.514 ± 0.282 (0.238 to 0.801). Conversely, when the ‘Const Trues’ framing scheme was applied, the results showed much smaller fluctuations with F = 78.038 ± 8.975 (86.450 to 68.590), P < 0.001 for all conditions and η2p = 0.730 ± 0.017 (0.742 to 0.710), and regions with significant effects were more robustly reproduced. Further, differences, which would indicate false positive identifications between HC and SZ groups in five brain regions when using the ‘Const 5 min’ framing scheme, were not observed with the ‘Const Trues’ framing.ConclusionsBased on an [11C]ABP688 PET study in SZ patients, the results show that non-consistent BPND outcomes can be propagated by the framing scheme and that potential bias can be minimized using ‘Const Trues’ framing.

Emergent external ventricular drain placement in patients with factor Xa inhibitor-associated intracerebral hemorrhage after reversal with andexanet alfa

BackgroundAndexanet alfa (AA), a factor Xa-inhibitor (FXi) reversal agent, is given as a bolus followed by a 2-hour infusion. This long administration time can delay EVD placement in intracerebral hemorrhage (ICH) patients. We sought to evaluate the safety of EVD placement immediately post-AA bolus compared to post-AA infusion. MethodsWe conducted a retrospective study that included adult patients admitted with FXi-associated ICH who received AA and underwent EVD placement The primary outcome was the occurrence of a new hemorrhage (tract, extra-axial, or intraventricular hemorrhage). Secondary outcomes included mortality, intensive care unit and hospital length of stay, and discharge modified Rankin Score. The primary safety outcome was documented thrombotic events. ResultsTwelve patients with FXi related ICH were included (EVD placement post-AA bolus, N = 8; EVD placement post-AA infusion, N = 4). Each arm included one patient with bilateral EVD placed. There was no difference in the incidence of new hemorrhages, with one post-AA bolus patient had small, focal, nonoperative extra-axial hemorrhage. Morbidity and mortality were higher in post-AA infusion patients (mRS, post-AA bolus, 4 [4–6] vs. post-AA infusion 6 [5,6], p = 0.24 and post-AA bolus, 3 (37.5 %) vs. post-AA infusion, 3 (75 %), p = 0.54, respectively). One patient in the post-AA bolus group had thrombotic event. There was no difference in hospital LOS (post-AA bolus, 19 days [12–26] vs. post-AA infusion, 14 days [9–22], p = 0.55) and ICU LOS (post-AA bolus, 10 days [6–13] vs. post-AA infusion, 11 days [5–21], p = 0.86). ConclusionWe report no differences in the incidence of tract hemorrhage, extra-axial hemorrhage, or intraventricular hemorrhage post-AA bolus versus post-AA infusion. Larger prospective studies to validate these results are warranted.

Abstract WMP3: A Five-minute Delay From Bolus Injection To Infusion Halves Plasma Concentration Of Tissue Plasminogen Activator

Objectives: Reducing the time between the onset of cerebral infarction and treatment with tissue plasminogen activator improves the prognosis of patients with cerebral infarction. Diverse dosing protocols have been developed with the aim of reducing the time to a bolus injection; however, only few studies have investigated the methods and effects of the interrupted time between bolus and postbolus infusion. Hence, we evaluated the impact of this interruption on pharmacokinetics. Materials and Methods: We calculated the changes in alteplase concentration after a bolus injection with high precision, in relation to different interval times. Simulations were performed using the linpk package of the statistical analysis software R. Postbolus infusion was initiated 0, 5, 15, or 30 min intervals after bolus dosing. The calculation interval was set as 6 s. Results: Alteplase concentration rose to 1.23 mg/ml following bolus dosing. However, it dropped to 0.53 mg/ml (43.4%) during a 5-min interval, 0.27 mg/ml (22.23%) during a 15-min interval, and 0.10 mg/ml (8.38%) during a 30-min interval. Conclusion: Because of the short half-life of alteplase, even a short delay in initiating postbolus infusion can cause a significant reduction in the serum alteplase concentration.

Systemic opioid regimens for postoperative pain in neonates.

Postoperative pain clinical management in neonates has always been a challenging medical issue. Worldwide, several systemic opioid regimens are available for pediatricians, neonatologists, and general practitioners to control pain in neonates undergoing surgical procedures. However, the most effective and safe regimen is still unknown in the current body of literature. To determine the effects of different regimens of systemic opioid analgesics in neonates submitted to surgery on all-cause mortality, pain, and significant neurodevelopmental disability. Potentially assessed regimens might include: different doses of the same opioid, different routes of administration of the same opioid, continuous infusion versus bolus administration, or 'as needed' administration versus 'as scheduled' administration. Searches were conducted in June 2022 using the following databases: Cochrane Central Register of Controlled Trials [CENTRAL], PubMed, and CINAHL. Trial registration records were identified via CENTRAL and an independent search of the ISRCTN registry. We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, and cross-over controlled trials evaluating systemic opioid regimens' effects on postoperative pain in neonates (pre-term or full-term). We considered suitable for inclusion: I) studies evaluating different doses of the same opioid; 2) studies evaluating different routes of administration of the same opioid; 3) studies evaluating the effectiveness of continuous infusion versus bolus infusion; and 4) studies establishing an assessment of an 'as needed' administration versus 'as scheduled' administration. According to Cochrane methods, two investigators independently screened retrieved records, extracted data, and appraised the risk of bias. We stratified meta-analysis by the type of intervention: studies evaluating the use of opioids for postoperative pain in neonates through continuous infusion versus bolus infusion and studies assessing the 'as needed' administration versus 'as scheduled' administration. We used the fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD), standardized mean difference (SMD), median, and interquartile range (IQR) for continuous data. Finally, we used the GRADEpro approach for primary outcomes to evaluate the quality of the evidence across included studies. In this review, we included seven randomized controlled clinical trials (504 infants) from 1996 to 2020. We identified no studies comparing different doses of the same opioid, or different routes. The administration of continuous opioid infusion versus bolus administration of opioids was evaluated in six studies, while one study compared 'as needed' versus 'as scheduled' administration of morphine given by parents or nurses. Overall, the effectiveness of continuous infusion of opioids over bolus infusion as measured by the visual analog scale (MD 0.00, 95% confidence interval (CI) -0.23 to 0.23; 133 participants, 2 studies; I² = 0); or using the COMFORT scale (MD -0.07, 95% CI -0.89 to 0.75; 133 participants, 2 studies; I² = 0), remains unclear due to study designs' limitations, such as the unclear risk of attrition, reporting bias, and imprecision among reported results (very low certainty of the evidence). None of the included studies reported data on other clinically important outcomes such as all-cause mortality rate during hospitalization, major neurodevelopmental disability, the incidence of severe retinopathy of prematurity or intraventricular hemorrhage, and cognitive- and educational-related outcomes. AUTHORS' CONCLUSIONS: Limited evidence is available on continuous infusion compared to intermittent boluses of systemic opioids. We are uncertain whether continuous opioid infusion reduces pain compared with intermittent opioid boluses; none of the studies reported the other primary outcomes of this review, i.e. all-cause mortality during initial hospitalization, significant neurodevelopmental disability, or cognitive and educational outcomes among children older than five years old. Only one small study reported on morphine infusion with parent- or nurse-controlled analgesia.

Valproic acid as adjuvant treatment for convulsive status epilepticus: a randomised clinical trial

BackgroundGeneralised convulsive status epilepticus (GCSE) is a medical emergency. Guidelines recommend a stepwise strategy of benzodiazepines followed by a second-line anti-seizure medicine (ASM). However, GCSE is uncontrolled in 20–40% patients and is associated with protracted hospitalisation, disability, and mortality. The objective was to determine whether valproic acid (VPA) as complementary treatment to the stepwise strategy improves the outcomes of patients with de novo established GCSE.MethodsThis was a multicentre, double-blind, randomised controlled trial in 244 adults admitted to intensive care units for GCSE in 16 French hospitals between 2013 and 2018. Patients received standard care of benzodiazepine and a second-line ASM (except VPA). Intervention patients received a 30 mg/kg VPA loading dose, then a 1 mg/kg/h 12 h infusion, whilst the placebo group received an identical intravenous administration of 0.9% saline as a bolus and continuous infusion. Primary outcome was proportion of patients discharged from hospital by day 15. The secondary outcomes were seizure control, adverse events, and cognition at day 90.ResultsA total of 126 (52%) and 118 (48%) patients were included in the VPA and placebo groups. 224 (93%) and 227 (93%) received a first-line and a second-line ASM before VPA or placebo infusion. There was no between-group difference for patients hospital-discharged at day 15 [VPA, 77 (61%) versus placebo, 72 (61%), adjusted relative risk 1.04; 95% confidence interval (0.89–1.19); p = 0.58]. There were no between-group differences for secondary outcomes.ConclusionsVPA added to the recommended strategy for adult GCSE is well tolerated but did not increase the proportion of patients hospital-discharged by day 15.Trial registration No. NCT01791868 (ClinicalTrials.gov registry), registered: 15 February 2012.

Tissue Distribution of Cisplatin by Intra-arterial Infusion Route in Comparison to Systemic Route: Implication to Therapy for Node-positive Bladder Cancer.

In clinical practice, platinum-based systemic chemotherapy works to shrink pelvic lymph nodes. Intra-arterial (IA) bolus infusion may result in more favorable results than systemic chemotherapy. In the present study, we investigated the distribution of cisplatin administrated by IA infusion in varying organs, specifically focusing on the node tissue, in comparison with the intravenous (IV) route. Under anesthesia, cisplatin 0.42 mg/body was administrated by IA or IV infusion in rats to mimic a balloon-occluded arterial infusion model used in clinical practice. The kidney, bladder, lymphatic tissue, and peripheral blood were extracted to analyze the amount of cisplatin by inductively coupled plasma-mass spectrometry. Concertation of cisplatin by IA infusion was higher than that by the IV route in the peripheral blood and kidney. IA infusion led to a significantly high concentration of cisplatin in the bladder compared to IV infusion (1.3±0.452 vs. 0.2 ppb/mg ± 0.055, p=0.050). Furthermore, the IA method led to an extremely high concentration of cisplatin in the lymphatic tissue compared to the IV method (0.1±0.036 vs. 13.3±5.36, p=0.048). High cisplatin accumulation in the lymphatic tissue and bladder by IA administration may have a potential role for treating patients with node-positive bladder cancer.

Risk stratification of extravasation during semi-automatic intraosseous device use in a pediatric emergency setting.

The semi-automatic intraosseous device (EZ-IO®) is useful for safely securing intraosseous access. There are some complications associated with its use but few studies have examined the risk factors. The present study aimed to investigate the risk factors for extravasation as a complication of EZ-IO use in pediatric patients. This study is a secondary analysis of a previous, monocentric, retrospective study conducted in Japan describing the use of EZ-IO in a pediatric emergency department. The patients included in the study were younger than 16 years of age with EZ-IO use at the Tokyo Metropolitan Children's Medical Center between January, 2013 and August, 2018. The factors analyzed included demographic information (sex, age, weight), Glasgow Coma Scale (GCS), diagnosis, bolus infusion, and lidocaine use. The primary endpoint was the odds ratio (OR) and 95% confidence interval (CI) for extravasation incidence. Seventy-two patients were enrolled; 14 of these had extravasation, 39 (54.2%) had a diagnosis of cardiac arrest, and 50 (69.4%) had a GCS score of 8 or less. Statistical analysis demonstrated that the group with a high GCS score was significantly associated with extravasation: GCS (<13) versus GCS (13≦) (OR: 12.25; 95% CI: 2.54-59.15; p < 0.01), GCS (<8) versus GCS (8≦) (OR: 4.78; 95% CI: 1.34-17.01; p = 0.03). A high GCS score was associated with extravasation in EZ-IO use significantly more often than a low GCS score. No significant difference was found in the other endpoints.

Pushing the agenda for intravenous push administration in outpatient parenteral antimicrobial therapy.

Intravenous push (IVP) antimicrobial administration refers to rapid bolus infusion of medication. This drug delivery method offers improved patient convenience, superior patient and nursing satisfaction, and cost savings when used in outpatient parenteral antimicrobial therapy (OPAT). Antimicrobial agents must demonstrate optimal physiochemical and pharmacologic characteristics, as well as sufficient syringe stability, to be administered in this manner. Additionally, impacts on medication tolerability, patient safety, and effectiveness must be considered. This narrative review summarizes the available data and practical implications of IVP administration of antimicrobials in the OPAT setting.

A prospective, randomized, interventional, comparative study between dexmedetomidine and propofol infusion for monitored anesthesia care during internal jugular vein chemoport insertion

Background: Chemotherapy through peripheral intravenous cannula causes severe thrombophlebitis. Chemoport is a best and favorable alternative for the same. It is done under local infiltration along with monitored anesthesia care with sedation. However, due to the lack of any fixed regimen, overt to under sedation is more common. To maintain an effective, consistent, and continuous level of sedation, we compared dexmedetomidine and propofol infusion in patients requiring monitored anesthesia care (MAC) for chemoport insertion. Methodology: Fifty patients posted for internal jugular vein chemoport insertion were randomly distributed into two groups: the propofol group and dexmedetomidine group. In Group P-injection, propofol infusion started at 125 μg/kg/min. Once observer's OAAS score 3 was achieved, propofol infusion was reduced to 25–75 μg/kg/min, whereas in Group D-Injection, dexmedetomidine bolus infusion was started at 1 μg/kg for 10 min and followed by 0.3–0.7 μg/kg/h and titrated to an OAAS score of 3. Results: OAAS score 3 was achieved significantly earlier in the propofol group as compared to the dexmedetomidine group (3.12 ± 1.7 vs. 8.04 ± 2.07, respectively). We were also able to maintain the desired sedation level throughout the procedure. Satisfaction scores in both the groups were comparable and patients in both the groups were hemodynamically stable throughout the procedure. Conclusion: In the current study, we found that propofol infusion was better regarding early onset and maintenance of OAAS score 3 with no requirement of rescue sedation during the procedure. The hemodynamic parameters and satisfaction scores were comparable in both groups. Hence, we suggest the use of injection propofol infusion for MAC under sedation in a patient requiring internal jugular vein chemoport insertion when compared to dexmedetomidine.

Effect of repeated bolus and continuous glucose infusion on a panel of circulating biomarkers in healthy volunteers.

Glycaemic variability (GV) refers to fluctuations in the blood glucose level and may contribute to complications in patients suffering from Diabetes. Several studies show negative effects of GV on the cardiovascular system, however there is still a lack of conclusive evidence. Using an explorative cardiovascular panel, it is possible to simultaneously measure the effects on proteins relevant for cardiovascular processes. The aim of this study was to investigate the effects of rapid glucose excursions on cardiovascular and metabolic parameters in healthy individuals. An explorative single-blinded cross-over study was performed in ten healthy men. Subjects received 3 times 20 grams of glucose i.v. over 5 minutes or 60 grams of glucose continuously over 3 hours. Blood was taken for repeated measurements of the cardiovascular panel over the following 6 hours and again after 24 and 48 hours. We observed a significant elevation of 7 cardiovascular biomarkers (BMP6, SLAMF7, LOX-1, ADAMTS13, IL-1RA, IL-4RA, PTX3) at t = 360min after rapid glucose infusion compared to a continuous glucose infusion. Intraday GV seems to have acute effects on cardiovascular proteins in healthy test persons. Rapid glucose administration compared to continuous administration showed significant changes in BMP6, SLAMF7, ADAMTS13, IL1RA, PTX3, IL-4RA and LOX-1. NCT04488848.

Comparison of Continuous and Programmed Intermittent Bolus Infusion of 0.2% Ropivacaine after Ultrasound-Guided Continuous Interscalene Brachial Plexus Block in Arthroscopic Shoulder Surgery.

Despite the clinical effectiveness of the programmed intermittent bolus (PIB) method for epidural analgesia, evidence for this method in continuous interscalene brachial plexus block (CIBPB) is unclear. This study aimed to investigate the pain relief effect after arthroscopic shoulder surgery according to the administration method by comparing the PIB and continuous infusion methods among the administration methods of local anesthetics. Sixty-four patients aged >19 years scheduled for elective arthroscopic shoulder surgery were enrolled and divided into two groups. Ultrasound-guided CIBPB was performed to control postoperative pain. The infusion pump was programmed so that 0.2% ropivacaine was continuously injected at 1.1 mL/h in group A, whereas in group B, 0.1 mL/h was continuously injected and 4 mL was periodically injected at 4 h intervals. In both groups, a further infusion of 4 mL of 0.2% ropivacaine was administered if the patient requested additional analgesia, and the lockout time was set at 30 min. Postoperative pain quality was assessed using a visual analog scale (VAS), and the incidence of patients requiring additional analgesics, motor blockade using a modified Bromage scale (MBS), and consumed doses of local anesthetic were assessed. The VAS and incidence of rescue analgesics were performed when the patient could communicate voluntarily after admission to the post-anesthetic care unit, and at 24 and 48 h after surgery showed no significant difference between the two groups. The MBS at 24 h after surgery was significantly higher in group B (p = 0.038). In the comparison of consumed doses of local anesthetic, group B had a significantly higher bolus injection dose (p = 0.047) and frequency of bolus use in the 24 h after surgery (p = 0.034). The PIB method in CIBPB after arthroscopic shoulder surgery provided a similar analgesic effect, with a higher bolus injection dose of local anesthetic and increased motor blockade than the continuous infusion method.

Comparative effectiveness and safety of bolus vs. continuous infusion of loop diuretics: Results from the MIMIC-III Database

BackgroundIt is unclear whether fluid management goals are best achieved by bolus injection or continuous infusion of loop diuretics. In this study, we compared the effectiveness and safety of a continuous infusion with that of a bolus injection when an increased loop diuretic dosage is required in intensive care unit (ICU) patients. MethodsWe obtained data from the MIMIC-III database for patients who were first-time ICU admissions and required an increased diuretic dosage. Patients were excluded if they had an estimated glomerular filtration rate <15 ml/min/1.73 m2, were receiving renal replacement therapy, had a baseline systolic blood pressure <80 mmHg, or required a furosemide dose <120 mg. The patients were divided into a continuous group and a bolus group. Propensity score matching was used to balance patients’ background characteristics. ResultsThe final dataset included 807 patients (continuous group, n = 409; bolus group, n = 398). After propensity score matching, there were 253 patients in the bolus group and 231 in the continuous group. The 24 h urine output per 40 mg of furosemide was significantly greater in the continuous group than in the bolus group (234.66 ml [95% confidence interval (CI) 152.13–317.18, p < 0.01]). There was no significant between-group difference in the incidence of acute kidney injury (odds ratio 0.96, 95% CI 0.66–1.41, p = 0.85). ConclusionsOur results indicate that a continuous infusion of loop diuretics may be more effective than a bolus injection and does not increase the risk of acute kidney injury in patients who need an increased diuretic dosage in the ICU.

Impact of the fluid challenge infusion rate on cardiac stroke volume during major spinal neurosurgery: a prospective single center randomized interventional trial

BackgroundFluid therapy, including the choice of a crystalloid or colloid infusion, the execution time of a volume bolus, and the expected volume need of a patient during surgery, varies greatly in clinical practice. Different goal directed fluid protocols have been developed, where fluid boluses guided by dynamic preload parameters are administered within a specific period.ObjectiveTo study the efficacy of two fluid bolus infusion rates measured by the response of hemodynamic parameters.DesignMonocentric randomized controlled interventional trial.SettingUniversity hospital.PatientsForty patients undergoing elective major spinal neurosurgery in prone position were enrolled, thirty-one were finally analyzed.InterventionsPatients were randomly assigned to receive 250 ml crystalloid and colloid boluses within 5 min (group 1) or 20 min (group 2) when pulse pressure variation (PPV) exceeded 14%.Main outcome measuresChanges in stroke volume (SV), mean arterial pressure (MAP), and catecholamine administration.ResultsGroup 1 showed a greater increase in SV (P = 0.031), and MAP (P = 0.014), while group 2 still had higher PPV (P = 0.005), and more often required higher dosages of noradrenalin after fluid administration (P = 0.033). In group 1, fluid boluses improved CI (P < 0.01), SV (P < 0.01), and MAP (P < 0.01), irrespective of whether crystalloids or colloids were used. In group 2, CI and SV did not change, while MAP was slightly increased (P = 0.011) only after colloid infusion.ConclusionsA fluid bolus within 5 min is more effective than those administered within 20 min and should therefore be the primary treatment option. Furthermore, bolus infusions administered within 20 min may result in volume overload without achieving relevant hemodynamic improvements.Trial registrationGerman Clinical Trials Register: DRKS00022917.

Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest: a randomized clinical trial

BackgroundPatients resuscitated from out-of-hospital cardiac arrest (OHCA) have a high morbidity and mortality risk and often develop post-cardiac arrest syndrome (PCAS) involving systemic inflammation. The severity of the inflammatory response is associated with adverse outcome, with anoxic irreversible brain injury as the leading cause of death following resuscitated OHCA. The study aimed to investigate the anti-inflammatory and neuroprotective effect of pre-hospital administration of a high-dose glucocorticoid following OHCA.MethodsThe study is an investigator-initiated, randomized, multicenter, single-blinded, placebo-controlled, clinical trial. Inclusion will continue until one hundred twenty unconscious OHCA patients surviving a minimum of 72 h are randomized. Intervention is a 1:1 randomization to an infusion of methylprednisolone 250 mg following a minimum of 5 min of sustained return of spontaneous circulation in the pre-hospital setting. Methylprednisolone will be given as a bolus infusion of 1 × 250 mg (1 × 4 mL) over a period of 5 min. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%). Main eligibility criteria are OHCA of presumed cardiac cause, age ≥ 18 years, Glasgow Coma Scale ≤ 8, and sustained ROSC for at least 5 min. Co-primary endpoint: Reduction of interleukin-6 and neuron-specific-enolase. Secondary endpoints: Markers of inflammation, brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, safety, neurological function at follow-up, and mortality. A research biobank is set up with blood samples taken daily during the first 72 h from hospitalization to evaluate primary and secondary endpoints.DiscussionWe hypothesize that early anti-inflammatory steroid treatment in the pre-hospital setting can mitigate the progression of PCAS following resuscitated OHCA. Primary endpoints will be assessed through analyses of biomarkers for inflammation and neurological damage taken during the first 72 h of admission.Trial registrationEudraCT number: 2020-000855-11; submitted March 30, 2020ClinicalTrials.gov Identifier: NCT04624776; submitted October 12, 2020, first posted November 10, 2020

Pharmacokinetic Modeling of Optimized Midazolam and Pentobarbital Dosing Used in Treatment Protocols of Refractory Status Epilepticus.

To model bolus dosing, infusion rate, and weaning rate on theoretical serum concentration of midazolam and pentobarbital used in the treatment of refractory status epilepticus (RSE). One- and two-compartment in silico pharmacokinetic models of midazolam and pentobarbital. Not applicable. Not applicable. We compared the model variables used in midazolam and pentobarbital protocols for standard RSE. Standard RSE treatment protocols result in steady-state serum concentrations that are 6.2-9.0-fold higher for the one-compartment model and 2.3-4.7-fold higher for the two-compartment model. In the model, not including bolus doses delays the achievement of serum steady-state concentration by 0.5 and 2.7 hours for midazolam and pentobarbital, respectively. Abrupt discontinuation of these medications reduces modeled medication exposure by 1.1 and 6.4 hours, respectively. Our in silico pharmacokinetic modeling of standard midazolam and pentobarbital dosing protocols for RSE suggests potential variables to optimize in future clinical studies.

A novel "double-dye" technique to determine the injectate spread of bolus versus continuous infusion in erector spinae plane block in cadavers.

A novel "double-dye" technique to determine the injectate spread of bolus versus continuous infusion in erector spinae plane block in cadavers.

Two pediatric cases of severe hemophilia A in which emicizumab prophylaxis failed to prevent traumatic extra-articular hemorrhage.

Emicizumab reduces bleeding episodes in patients with severe hemophilia A (PwHA). Little information is available on hemostatic management of severe traumatic hemorrhages in emicizumab-treated pediatric PwHA. We assessed therapeutic efficacy and global coagulation potentials in two pediatric cases of emicizumab-treated pediatric PwHA with intracranial or retroperitoneal/iliopsoas hemorrhage. A modified clot waveform analysis (CWA) triggered by mixtures of tissue factor and ellagic acid was used to assess coagulant potentials, and maximum coagulant velocity (Ad|min1|) was calculated. One patient with intracranial hemorrhage was treated with continuous infusions of recombinant factor VIII (rFVIII) at a dose of 4-4.6IU/kg/hr for 9days, followed by bolus infusion at 66IU/kg/day for 2days and 33IU/kg/day for an additional 2days. The Ad|min1| was increased from 5.5 (at baseline) to 7.0-8.1 under concomitant treatment and maintained within or near normal range (IQR; 6.9-7.7). The other patient with retroperitoneal/iliopsoas hemorrhage received bolus infusions of rFVIII at 50IU/kg/day for 20days and every-other-day infusion of rFVIII for 8days. The Ad|min1| was increased from 5.2 (at baseline) to 5.8-6.8 under concomitant treatment and maintained within the normal range. We successfully managed a treatment plan for severe traumatic bleeding in emicizumab-treated pediatric PwHA using modified CWA.