The Drug Titration Paradox: Correlation of More Drug With Less Effect in Clinical Data.

While analyzing clinical data where an anesthetic was titrated based on an objective measure of drug effect, we observed paradoxically that greater effect was associated with lesser dose. With this study we sought to find a mathematical explanation for this negative correlation between dose and effect, to confirm its existence with additional clinical data, and to explore it further with Monte Carlo simulations. Automatically recorded dosing and effect data from more than 9,000 patients was available for the analysis. The anesthetics propofol and sevoflurane and the catecholamine norepinephrine were titrated to defined effect targets, i.e., the processed electroencephalogram (Bispectral Index, BIS) and the blood pressure. A proportional control titration algorithm was developed for the simulations. We prove by deduction that the average dose-effect relationship during titration to the targeted effect will associate lower doses with greater effects. The finding of negative correlations between propofol and BIS, sevoflurane and BIS, and norepinephrine and mean arterial pressure confirmed the titration paradox. Monte Carlo simulations revealed two additional factors that contribute to the paradox. During stepwise titration toward a target effect, the slope of the dose-effect data for the population will be "reversed," i.e., the correlation between dose and effect will not be positive, but will be negative, and will be "horizontal" when the titration is "perfect." The titration paradox must be considered whenever data from clinical titration (flexible dose) studies are interpreted. Such data should not be used naively for the development of dosing guidelines.

Sevoflurane Consumption During Inhalational Induction in Children: A Randomized Comparison of Minute Ventilation-Based Techniques With Standard Fixed Fresh Gas Flow Technique.

This study was done to ascertain the optimum fresh gas flow (FGF) offering the best balance between rapid induction and minimal waste in pediatric patients. Forty-five children (weighing 10-20 kg) undergoing elective procedures under general anesthesia were randomly assigned into 3 groups: 0.5 minute ventilation (MV), MV, and S (FGF = 6 L/min). After priming the pediatric closed circuit, anesthesia was induced using a face mask with 8% sevoflurane in 100% oxygen (Draeger Primus Vista 120 anesthesia machine) at FGF-determined MV per group allocation. After loss of eyelash reflex (time 1 [T1]), intravenous cannulation (T2) and laryngeal mask airway (LMA) placement (T3) were done. Total sevoflurane consumed during induction (measured using logbook function) was the primary outcome. The cost of sevoflurane, any reflex movement, tachycardia (heart rate change > 20%), or additional propofol boluses required were also recorded. Sevoflurane consumption (3.8 vs 5.8 vs 9.2 mL) and cost of sevoflurane (104.2 vs 199.4 vs 312.8 rupees) were lowest in group 0.5 MV (P < .001). There was no difference in hemodynamic parameters, movement on cannulation/LMA insertion, and rescue propofol boluses required. For pediatric sevoflurane induction, half the MV-based FGF provided similar anesthetic conditions for LMA insertion with minimum sevoflurane consumption.

Estimating the Impact of Carbon Dioxide Absorbent Performance Differences on Absorbent Cost During Low-Flow Anesthesia.

BACKGROUND: Reducing fresh gas flow when using a circle anesthesia circuit is the most effective strategy for reducing both inhaled anesthetic vapor cost and waste. As fresh gas flow is reduced, the amount of exhaled gas rebreathed increases, but the utilization of carbon dioxide absorbent increases as well. Reducing fresh gas flow may not make economic sense if the increased cost of absorbent utilization exceeds the reduced cost of anesthetic vapor. The primary objective of this study was to determine the minimum fresh gas flow at which absorbent costs do not exceed vapor savings. Another objective is to provide a qualitative insight into the factors that influence absorbent performance as fresh gas flow is reduced. METHODS: A mathematical model was developed to compare the vapor savings with the cost of carbon dioxide absorbent as a function of fresh gas flow. Parameters of the model include patient size, unit cost of vapor and carbon dioxide absorbent, and absorbent capacity and efficiency. Boundaries for fresh gas flow were based on oxygen consumption or a closed-circuit condition at the low end and minute ventilation to approximate an open-circuit condition at the high end. Carbon dioxide production was estimated from oxygen consumption assuming a respiratory quotient of 0.8. RESULTS: For desflurane, the cost of carbon dioxide absorbent did not exceed vapor savings until fresh gas flow was almost equal to closed-circuit conditions. For sevoflurane, as fresh gas flow is reduced, absorbent costs increase more slowly than vapor costs decrease so that total costs are still minimized for a closed circuit. Due to the low cost of isoflurane, even with the most effective absorbent, the rate of absorbent costs increase more rapidly than vapor savings as fresh gas flow is reduced, so that an open circuit is least expensive. The total cost of vapor and absorbent is still lowest for isoflurane when compared with the other agents. CONCLUSIONS: The relative costs of anesthetic vapor and carbon dioxide absorbent as fresh gas flow is reduced are dependent on choice of anesthetic vapor and performance of the carbon dioxide absorbent. Absorbent performance is determined by the product selected and strategy for replacement. Clinicians can maximize the performance of absorbents by replacing them based on the appearance of inspired carbon dioxide rather than the indicator. Even though absorbent costs exceed vapor savings as fresh gas flow is reduced, isoflurane is still the lowest cost choice for the environmentally sound practice of closed-circuit anesthesia.

Perioperative interdisciplinary approach for reduction of opioid use in pediatric tonsillectomy: Protocol using dexmedetomidine and bupivicaine as adjunct agents.

IMPORTANCE: Pediatric tonsillectomy is a common procedure now being performed most often for patients with obstructive sleep apnea, which has been associated with increased sensitivity to the respiratory side effects of opioid medications. This study investigates a strategy to decrease the use of opiate medications in a particularly vulnerable population. OBJECTIVE: Describe an interdisciplinary approach between Otolaryngologists and Anesthesiologists to decrease opiate use in tonsillectomy patients. Demonstrate safety of this protocol. Evaluate the effect of the protocol on intraoperative need for opiate medications and inhaled anesthetic use. Perform cost analysis of the protocol. DESIGN: Retrospective case-control study with cost analysis. SETTING: Tertiary Care Hospital. PARTICIPANTS: Pediatric patients undergoing tonsillectomy at a tertiary care hospital. INTERVENTIONS: Preoperative and intraoperative dexmedetomidine with local bupivacaine injection into the tonsillar fossa. MEASURES: Intraoperative need for sevoflurane, opiate, and propofol. Post-operative pain scores, and utilization of post-operative opiate, acetaminophen, and ibuprofen pain medications. Post-operative adverse events. Cost analysis of protocol. RESULTS: This protocol led to a decrease in intraoperative opiate use by 49.6%, a decrease in intraoperative sevofluorane use by 18%, and a lower reported maximum post-operative pain score without any increase in adverse events. The protocol added a small increase in medication cost of $4.07 to each procedure. CONCLUSION: The use of dexmedetomidine and local anesthetic in pediatric tonsillectomy is a safe and effective protocol that allows for the reduction of opiate use and improved post-operative pain control. KEY POINTS: Question: Can the combination of dexmedetomidine and infiltration of local anesthetic reduce overall opioid use for peediatric patients undergoing tonsillectomy? FINDINGS: In this case-control study, use of dexmedetomidine and local anesthetic injected into the tonsillar fossa led to a decrease in intraoperative opiate use by 49.6%, a decrease in intraoperative sevofluorane use by 18%, and a lower reported maximum pain score without an increase in adverse events. Meaning: Use of dexmedetomidine and local anesthetic as anesthetic adjuncts may help reduce need for intraoperative opiates and decrease the use of volatile anesthetic agents in pediatric tonsillectomy patients, which are undesirable medications in the pediatric population for their respective respiratory depression and potentially neurotoxic side effects.

Comparison of low-fresh gas flow technique to standard technique of sevoflurane induction in children-A randomized controlled trial.

BACKGROUND: Although sevoflurane is preferred for inhalational induction in children, financial and environmental costs remain major limitations. The aim of this study was to determine if the use of low-fresh gas flow during inhalational induction with sevoflurane could significantly reduce agent consumption, without adversely affecting induction conditions. METHODS: After institutional ethical committee approval, 50 children, aged 1-5 years, undergoing ophthalmic procedures under general anesthesia, were randomized into two groups-standard induction (Group S) and low-flow induction (Group L). A pediatric circle system with 1 L reservoir bag was primed with 8% sevoflurane in oxygen at 6 L min-1 for 30 seconds before beginning induction. In Group S, fresh gas flow was maintained at 6 L min-1 until the end of induction. In Group L, fresh gas flow was reduced to 1 L min-1 after applying facemask (time = T0). In both groups, sevoflurane was reduced to 5% after loss of eyelash reflex (T1). Once adequate depth of anesthesia was achieved (regular respiration, loss of muscle tone, and absence of movement to trapezius squeeze), intravenous access was secured (T2), followed by insertion of an appropriately sized LMA-Classic™ (T3). Heart rate and endtidal sevoflurane concentration were measured at each of the above time points, and at 15 seconds following laryngeal mask airway insertion (T4). The total amount of sevoflurane consumed during induction was recorded. RESULTS: Sevoflurane consumption was significantly lower in Group L (4.17 ± 0.70 mL) compared to Group S (8.96 ± 1.11 mL) (mean difference 4.79 [95% CI = 4.25-5.33] mL; P < 0.001). Time to successful laryngeal mask airway insertion was similar in both groups. There were no significant differences in heart rate, incidence of reflex tachycardia, or need for rescue propofol. CONCLUSION: Induction of anesthesia with sevoflurane using low-fresh gas flow is effective in reducing sevoflurane consumption, without compromising induction time and conditions.

On-table extubation in neonates undergoing anoplasty: an experience of anesthetic management on the concept of fast-tracking anesthesia: A pilot study.

Fast-track anesthesia (FTA) is difficult to achieve in neonates due to immature organ function and high rates of perioperative events. As a high-risk population, neonates require prolonged postoperative mechanical ventilation, which may lead to contradictions in cases where neonatal intensive care unit resources and ventilator facilities are limited. The choice of anesthesia strategy and anesthetic can help achieve rapid postoperative rehabilitation and save hospitalization costs. The authors describe their experience with maintaining spontaneous breathing in neonates undergoing anoplasty without opioids or muscle relaxants.This retrospective chart review included neonates who underwent anoplasty in the authors' institution. Twelve neonates who underwent the procedure with atomized 5% lidocaine topical anesthesia around the glottis, combined with sevoflurane sedation and caudal anesthesia facilitating tracheal intubation without opioid and muscle relaxant comprised the FTA group. Ten neonates who underwent the intervention with routine anesthesia techniques in the same period comprised the control group (group C).The surgical success rate in the FTA group was 91.7%. There were no severe complications related to lidocaine administered around the glottis. Extubation time was significantly shorter in the FTA group than in group C (4 [2.5, 5.2] vs 81.5 [60.6, 96.8], respectively; P < .01). The duration of stay in the surgical intensive care unit (SICU) was longer in group C than in the FTA group (2 [2.0, 2.6] vs 1 [0.9, 2.0], respectively; P = .006,). A statistically significant lower rate of extubation-cough was noted after endotracheal tube removal in the FTA group compared with group C (18% vs 90%, respectively; P < .001). There was no difference in the duration of anesthesia or hospitalization costs between the 2 groups. No neonates required re-intubation after extubation.On-table extubation via 5% atomized lidocaine topical anesthesia around the glottis for tracheal intubation combined with sevoflurane sedation and caudal anesthesia without opioid and muscle relaxant was feasible in neonates undergoing anoplasty. This reduced time to extubation, length of SICU stay and saved resources. A similar trend in cost savings was also found; nevertheless, more studies are needed to confirm these results.

Choosing the optimal method of anaesthesia in anterior resection of the rectum procedures - assessment of the stress reaction based on selected hormonal parameters.

INTRODUCTION: The aim of this study was to compare hormonal stress responses (changes in adrenaline, noradrenaline, and cortisol concentrations) to surgical injury during total intravenous propofol anaesthesia and volatile anaesthesia with sevoflurane in patients subjected to anterior resection of the rectum. MATERIAL AND METHODS: The prospective randomised study included 61 patients qualified for anterior resection of the rectum. The subjects were randomised into two groups, based on the type of anaesthesia: 1) Group I (TIVA, n = 31), administered total intravenous propofol anaesthesia, and 2) Group II (VIMA, n = 30), administered volatile induction and maintenance sevoflurane anaesthesia. Serum concentra-tions of adrenaline, noradrenaline, and cortisol were determined prior to surgery, during assessment of abdominal cavity, after resection of the rectum, and 30 min and one day post-surgery. RESULTS: The two groups did not differ significantly in terms of their haemodynamic parameters: heart rate and arterial blood pressure. Compared to individuals subjected to TIVA, patients from the VIMA group presented with significantly higher concentrations of adrenaline during evaluation of the abdominal organs. No significant intergroup differences were found in terms of intra- and postoperative serum concentrations of noradrenaline and cortisol. CONCLUSIONS: TIVA and VIMA induce similar hormonal stress responses during anterior resection of the rectum. The increase in serum adrenaline concentration during evaluation of the abdominal organs in the VIMA group implies that the dose of sevoflurane should be escalated at this time point.