Assessment of the antinociceptive effect of a single fentanyl bolus dose in children: A pharmacokinetic and pharmacodynamic analysis based on the nociception level index during sevoflurane general anesthesia.

BACKGROUND: The Nociception Level Index has shown benefits in estimating the nociception/antinociception balance in adults, but there is limited evidence in the pediatric population. Evaluating the index performance in children might provide valuable insights to guide opioid administration. AIMS: To evaluate the Nociception Level Index ability to identify a standardized nociceptive stimulus and the analgesic effect of a fentanyl bolus. Additionally, to characterize the pharmacokinetic/pharmacodynamic relationship of fentanyl with the Nociception Level Index response during sevoflurane anesthesia. METHODS: Nineteen children, 5.3 (4.1-6.7) years, scheduled for lower abdominal or urological surgery, were studied. After sevoflurane anesthesia and caudal block, a tetanic stimulus (50 Hz, 60 mA, 5 s) was performed in the forearm. Following the administration of fentanyl 2 µg/kg intravenous bolus, three similar consecutive tetanic stimuli were performed at 5-, 15-, and 30-min post-fentanyl administration. Changes in the Nociception Level Index, heart rate, mean arterial pressure, and bispectral index were compared in response to the tetanic stimuli. Fentanyl plasma concentrations and the Nociception Level Index data were used to elaborate a pharmacokinetic/pharmacodynamic model using a sequential modeling approach in NONMEM®. RESULTS: After the first tetanic stimulus, both the Nociception Level Index and the heart rate increased compared to baseline (8 ± 7 vs. 19 ± 10; mean difference (CI95) -12(-18--6) and 100 ± 10 vs. 102 ± 10; -2(-4--0.1)) and decrease following fentanyl administration (19 ± 10 vs. 8 ± 8; 12 (5-18) and 102 ± 10 vs. 91 ± 11; 11 (7-16)). In subsequent tetanic stimuli, heart rate remained unchanged, while the Nociception Level Index progressively increased within 15 min to values similar to those before fentanyl. An allometric weight-scaled, 3-compartment model best characterized the pharmacokinetic profile of fentanyl. The pharmacokinetic/pharmacodynamic modeling analysis revealed hysteresis between fentanyl plasma concentrations and the Nociception Level Index response, characterized by plasma effect-site equilibration half-time of 1.69 (0.4-2.9) min. The estimated fentanyl C50 was 1.93 (0.73-4.2) ng/mL. CONCLUSION: The Nociception Level Index showed superior capability compared to traditional hemodynamic variables in discriminating different nociception-antinociception levels during varying fentanyl concentrations in children under sevoflurane anesthesia.

Comparison of sevoflurane concentration for insertion of proseal laryngeal mask airway and tracheal intubation in children (correlation with BIS) / Comparação da concentração de sevoflurano para a inserção de ML proseal e intubação traqueal em crianças (correlação com BIS)

BACKGROUND: Sevoflurane is an inhalational agent of choice in paediatric anaesthesia. For management of airways in children a suitable alternative to ETT is a paediatric proseal laryngeal mask airway (benchmark second generation SAD). Various studies have shown that less sevoflurane concentration is required for LMA insertion in comparison to TI. BIS is a useful monitor of depth of anaesthesia. AIMS: To compare concentration of sevoflurane (end tidal and MAC value) required for proseal laryngeal mask airway insertion and tracheal intubation in correlation with BIS index. METHOD: The prospective randomised single blind study was done in children between 2 and 9 years of ASA I and II and they were randomly allocated to Group P (proseal laryngeal mask airway insertion) and Group TI (tracheal intubation). No sedative premedication was given. Induction was done with 8% sevoflurane and then predetermined concentration was maintained for 10 min. Airway was secured either by proseal laryngeal mask airway or endotracheal tube without using muscle relaxant. End tidal sevoflurane concentration, MAC, BIS, and other vital parameters were monitored every minute till insertion of an airway device. Insertion conditions were observed. Statistical analysis was done by ANOVA and Students t test. RESULTS: Difference between ETLMI (2.49 ± 0.44) and ETTI (2.81 ± 0.65) as well as MACLMI (1.67 ± 0.13) and MACTI (1.77 ± 0.43) was statistically very significant, while BISLMI (49.05 ± 10.76) and BISTI (41.25 ± 3.25) was significant. Insertion conditions were comparable in both the groups. CONCLUSION: We can conclude that in children airway can be secured safely with proseal laryngeal mask airway using less sevoflurane concentration in comparison to tracheal intubation and this was supported by BIS index.

JUSTIFICATIVA: Sevoflurano é um agente inalatório de escolha em anestesia pediátrica. Para o manejo de vias aéreas em crianças, uma opção adequada para o TET é uma MLP pediátrica (referência de segunda geração SAD). Vários estudos mostraram que uma menor concentração do sevoflurano é necessária para a inserção da ML em comparação com a IT. O BIS é um monitor útil da profundidade da anestesia. OBJETIVOS: Comparar a concentração de sevoflurano (valores no fim da expiração e da CAM) necessária para a inserção de MLP e intubação traqueal em correlação com o BIS. MÉTODO: Estudo prospectivo, randômico e cego conduzido com crianças entre 2-9 anos, estado físico ASA I-II, randomicamente alocados nos grupos P (inserção de MLP) e IT (intubação traqueal). Pré-medicação sedativa não foi administrada. A indução foi feita com sevoflurano a 8% e, em seguida, a concentração predeterminada foi mantida durante 10 minutos. A via aérea foi garantida por MLP ou tubo endotraqueal, sem o uso de relaxante muscular. A concentração de sevoflurano no fim da expiração, CAM, BIS e outros parâmetros vitais foram monitorados a cada minuto até a inserção do dispositivo respiratório. As condições de inserção foram observadas. A análise estatística foi feita com o teste t de Student e Anova. RESULTADOS: As diferenças entre TEIML (2,49 ± 0,44) e TEIT (2,81 ± 0,65), bem como CAMIML (1,67 ± 0,13) e CAMIT (1,77 ± 0,43), foram estatisticamente muito significativas; enquanto BISIML (49,05 ± 10,76) e BISIT (41,25 ± 3,25) foram significativos. As condições de inserção foram comparáveis em ambos os grupos. CONCLUSÃO: Podermos concluir que a MLP em comparação com a intubação traqueal pode ser segura para a via aérea de crianças com o uso de menos concentração de sevoflurano, o que foi confirmado pelo BIS.

Comparison of sevoflurane concentration for insertion of proseal laryngeal mask airway and tracheal intubation in children (correlation with BIS).

BACKGROUND: Sevoflurane is an inhalational agent of choice in paediatric anaesthesia. For management of airways in children a suitable alternative to ETT is a paediatric proseal laryngeal mask airway (benchmark second generation SAD). Various studies have shown that less sevoflurane concentration is required for LMA insertion in comparison to TI. BIS is a useful monitor of depth of anaesthesia. AIMS: To compare concentration of sevoflurane (end tidal and MAC value) required for proseal laryngeal mask airway insertion and tracheal intubation in correlation with BIS index. METHOD: The prospective randomised single blind study was done in children between 2 and 9 years of ASA I and II and they were randomly allocated to Group P (proseal laryngeal mask airway insertion) and Group TI (tracheal intubation). No sedative premedication was given. Induction was done with 8% sevoflurane and then predetermined concentration was maintained for 10 min. Airway was secured either by proseal laryngeal mask airway or endotracheal tube without using muscle relaxant. End tidal sevoflurane concentration, MAC, BIS, and other vital parameters were monitored every minute till insertion of an airway device. Insertion conditions were observed. Statistical analysis was done by ANOVA and Students t test. RESULTS: Difference between ETLMI (2.49 ± 0.44) and ETTI (2.81 ± 0.65) as well as MACLMI (1.67 ± 0.13) and MACTI (1.77 ± 0.43) was statistically very significant, while BISLMI (49.05 ± 10.76) and BISTI (41.25 ± 3.25) was significant. Insertion conditions were comparable in both the groups. CONCLUSION: We can conclude that in children airway can be secured safely with proseal laryngeal mask airway using less sevoflurane concentration in comparison to tracheal intubation and this was supported by BIS index.

Correlation of bispectral index (BIS) monitoring and end-tidal sevoflurane concentration in a patient with lobar holoprosencephaly.

OBJECTIVE: The bispectral index (BIS) is a parameter derived by electroencephalography (EEG) which provides a direct measurement of the effects of sedatives and anesthetics on the brain and offers guidance on the adequacy of anesthesia. The literature lacks studies on BIS monitoring in pediatric patients with congenital brain disease undergoing general anesthesia. CLINICAL FEATURES: A 13-year-old child weighing 32kg, suffering from lobar holoprosencephaly, underwent surgery in which the bispectral index (BIS) monitoring the depth of anesthesia showed an abnormal response. Detailed analysis of the trends of BIS values in the different observation times demonstrated sudden falls and repetitive values of BIS likely related to repetitive epileptiform electrical activity caused by sevoflurane. CONCLUSION: The BIS is a very useful monitoring tool for assessing the degree of depth of anesthesia and to analyze the electroencephalographic variations of anesthetics. Particular attention should be given to patients with congenital disorders of the central nervous system in which the BIS may give abnormal responses that do not reflect an accurate assessment of the depth of anesthesia.

Obesity does not influence the onset and offset of sevoflurane effect as measured by the hysteresis between sevoflurane concentration and bispectral index.

BACKGROUND: The onset and offset of action of anesthetic gases might be delayed by respiratory changes and gas exchange alterations present in obese patients. In this study, we assessed the influence of obesity on the hysteresis between sevoflurane and its effect as measured by the bispectral index (BIS). Because the use of positive end-expiratory pressure (PEEP) in obese patients has improved gas exchange, we also assessed the influence of PEEP on hysteresis. METHODS: Fifteen obese and 15 normal-weight patients, ASA physical status I and II, 20 to 50 years old, scheduled to undergo general anesthesia for elective laparoscopic surgery, were prospectively studied. Anesthesia was induced with propofol and maintained with sevoflurane and fentanyl. At the end of surgery and after stable BIS values of 60 to 65, the inspired concentration of sevoflurane was increased to 5 vol% for 5 minutes or until BIS was <40 and then decreased. Sevoflurane transitions were performed once in normal-weight subjects (without PEEP) and twice in obese patients (one without PEEP and one with a PEEP of 8 cm H(2)O). The hysteresis between sevoflurane end-tidal concentrations and BIS during these transition periods was modeled with an inhibitory Emax model using a population pharmacokinetic/ pharmacodynamic (PK/PD) approach with NONMEM VI. A descriptive analysis of sevoflurane inspired and expired concentrations, BIS values, and time to reach different BIS end points was also used to compare the PK and PD characteristics. RESULTS: All patients completed the study. The data were adequately fit with the PK/PD model. The hysteresis expressed as the effect-site elimination rate constant was not influenced by body mass index or PEEP (P > 0.05). Neither obesity nor PEEP showed any influence on the PK/PD descriptors. CONCLUSIONS: Our results do not support the hypothesis that obesity prolongs induction or recovery times when sevoflurane, a poorly soluble anesthetic, is used to maintain anesthesia from 90 to 120 minutes.

Effect of lidocaine on the minimum alveolar concentration of sevoflurane in dogs.

OBJECTIVE: To investigate the effects of a low-dose constant rate infusion (LCRI; 50 microg kg(-1) minute(-1)) and high-dose CRI (HCRI; 200 microg kg(-1) minute(-1)) lidocaine on arterial blood pressure and on the minimum alveolar concentration (MAC) of sevoflurane (Sevo), in dogs. STUDY DESIGN: Prospective, randomized experimental design. ANIMALS: Eight healthy adult spayed female dogs, weighing 16.0 +/- 2.1 kg. METHODS: Each dog was anesthetized with sevoflurane in oxygen and mechanically ventilated, on three separate occasions 7 days apart. Following a 40-minute equilibration period, a 0.1-mL kg(-1) saline loading dose or lidocaine (2 mg kg(-1) intravenously) was administered over 3 minutes, followed by saline CRI or lidocaine LCRI or HCRI. The sevoflurane MAC was determined using a tail clamp. Heart rate (HR), blood pressure and plasma concentration of lidocaine were measured. All values are expressed as mean +/- SD. RESULTS: The MAC of Sevo was 2.30 +/- 0.19%. The LCRI reduced MAC by 15% to 1.95 +/- 0.23% and HCRI by 37% to 1.45 +/- 0.21%. Diastolic and mean pressure increased with HCRI. Lidocaine plasma concentration was 0.84 +/- 0.18 for LCRI and 1.89 +/- 0.37 microg mL(-1) for HCRI. Seventy-five percent of HCRI dogs vomited during recovery. CONCLUSION AND CLINICAL RELEVANCE: Lidocaine infusions dose dependently decreased the MAC of Sevo, did not induce clinically significant changes in HR or arterial blood pressure, but vomiting was common during recovery in HCRI.

Sevofluorano: un paso más en la búsqueda del anestésico inhalatorio ideal / Sevofluorane: another stage in the search of the ideal inhalatory anesthetic

El sevofluorano, un isopropil metil eter fluorinado, es un potente anestésico inhalatorio halogenado de amplio uso actualmente en Japón. Sus partículas características farmacocinéticas farmacodinámicas lo aproximan al anestésico inhalatorio ideal y lo hacen apto para la mayoría de las situaciones quirúrgicas, incluso muchas que hoy se presentan como un desafío para los anestesiólogos en su práctica diaria. Su pronta incorporación al arsenal anestesiológico obliga al profesional a un acabado conocimiento del mismo

Sevofluorano: un paso más en la búsqueda del anestésico inhalatorio ideal / Sevofluorane: another stage in the search of the ideal inhalatory anesthetic

El sevofluorano, un isopropil metil eter fluorinado, es un potente anestésico inhalatorio halogenado de amplio uso actualmente en Japón. Sus partículas características farmacocinéticas farmacodinámicas lo aproximan al anestésico inhalatorio ideal y lo hacen apto para la mayoría de las situaciones quirúrgicas, incluso muchas que hoy se presentan como un desafío para los anestesiólogos en su práctica diaria. Su pronta incorporación al arsenal anestesiológico obliga al profesional a un acabado conocimiento del mismo