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The Impact of Age on Propofol Requirement for Inducing Loss of Consciousness in Elderly Surgical Patients.

ABSTRACT: It is generally accepted that geriatric patients are more sensitive to propofol than adults; thus, a dose-adjusted propofol is recommended for these patients during the induction of anesthesia. However, for patients aged 75 years and over, established guidelines for propofol induction doses do not provide dose references. To this end, we observed 80 surgical patients (female 39, male 41, American Society of Anesthesiologists physical status score I ∼ II) to access the appropriate dose of propofol for inducing loss of consciousness (LOC). Accordingly, patients were subdivided into group A (20 patients, 45-64 years), group B (20 patients, 65-74 years), group C (20 patients, 75-84 years), and group D (20 patients, ≥ 85 years). All patients received propofol (at a rate of 0.3 mg/kg/min) alone for inducing LOC, which was defined by loss of both eyelash reflex and verbal response. Compared with group A, the propofol requirement for LOC in Group B, C and D decreased by 14.8, 25.2 and 38.5%, respectively. Bivariate linear correlation analysis showed that propofol requirement was negatively correlated with age. After adjusting for potential confounders, age was still an independent factor affecting propofol requirement. In conclusion, the propofol requirement for inducing LOC decreased significantly in elderly patients. We demonstrated that age was an independent factor impacting propofol requirement for LOC during the induction of general anesthesia, implying that the propofol dose for anesthesia induction should be further reduced in elderly surgical patients, especially those aged 75 years and over.

SUBMITTER: Yang H

PROVIDER: S-EPMC8996377 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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The Impact of Age on Propofol Requirement for Inducing Loss of Consciousness in Elderly Surgical Patients.

Yang Hua H Deng Hui-Min HM Chen Hai-Yan HY Tang Shu-Heng SH Deng Fang F Lu Yu-Gang YG Song Jin-Chao JC

Frontiers in pharmacology 20220328

It is generally accepted that geriatric patients are more sensitive to propofol than adults; thus, a dose-adjusted propofol is recommended for these patients during the induction of anesthesia. However, for patients aged 75 years and over, established guidelines for propofol induction doses do not provide dose references. To this end, we observed 80 surgical patients (female 39, male 41, American Society of Anesthesiologists physical status score I ∼ II) to access the appropriate dose of propofo ...[more]

PMID: 35418861

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Project description:BackgroundOlder people are more vulnerable to hemodynamic instability caused by propofol due to their decreased initial distribution volume and increased sensitivity to propofol. Midazolam or remifentanil can often be coadministered because of their synergistic or additive effects with propofol as well as amnesic properties and the blockade of sympathetic stimulation. However, no study has confirmed the appropriate dose of propofol for loss of consciousness in aged patients when administered with other drugs, including opioids or benzodiazepines.MethodsPatients >65 years scheduled for general anesthesia were enrolled. The patients were randomized into 3 groups using a computer-generated randomization table. Patients in group P (propofol) received only propofol for loss of consciousness, those in group PR (propofol-remifentanil) received remifentanil before propofol, and those in group PMR (propofol-midazolam-remifentanil) received remifentanil and midazolam before propofol. After propofol administration, loss of both eyelash reflex and verbal response represented success. The 95% effective dose of propofol for loss of consciousness in each group, which was the primary outcome, was determined using a modified biased coin up-and-down method.ResultsIn total, 120 patients were randomized into the 3 groups (n = 40). The 95% effective dose of propofol for loss of consciousness was 1.13, 0.87, and 0.72 mg/kg in groups P, PR, and PMR, respectively. The mean blood pressure (MBP) in group PMR was more significantly decreased before propofol injection (P = .041) as well as 2 minutes (P = .005) and 3 minutes after propofol administration (P<.001), compared with group P, but there were no intergroup differences at other time points.ConclusionsThe effective dose of propofol for loss of consciousness in elderly patients could be decreased by 23% and 36% when remifentanil pretreatment was used without and with midazolam, respectively. However, the decrease in MBP was greater with remifentanil and midazolam pretreatment than with propofol alone. These findings suggest that pretreatment with midazolam for propofol infusions with remifentanil in elderly patients should be cautiously used, due to hemodynamic instability during induction.

Project description:BackgroundInduction of general anesthesia with propofol induces radical changes in cortical network organization, leading to unconsciousness. While perioperative frontal electroencephalography (EEG) has been widely implemented in the past decades, validated and age-independent EEG markers for the timepoint of loss of consciousness (LOC) are lacking. Especially the appearance of spatially coherent frontal alpha oscillations (8-12 Hz) marks the transition to unconsciousness.Here we explored whether decomposing the EEG spectrum into its periodic and aperiodic components unveiled markers of LOC and investigated their age-dependency. We further characterized the LOC-associated alpha oscillations by parametrizing the adjusted power over the aperiodic component, the center frequency, and the bandwidth of the peak in the alpha range.MethodsIn this prospective observational trial, EEG were recorded in a young (18-30 years) and an elderly age-cohort (≥ 70 years) over the transition to propofol-induced unconsciousness. An event marker was set in the EEG recordings at the timepoint of LOC, defined with the suppression of the lid closure reflex. Spectral analysis was conducted with the multitaper method. Aperiodic and periodic components were parametrized with the FOOOF toolbox. Aperiodic parametrization comprised the exponent and the offset. The periodic parametrization consisted in the characterization of the peak in the alpha range with its adjusted power, center frequency and bandwidth. Three time-segments were defined: preLOC (105 - 75 s before LOC), LOC (15 s before to 15 s after LOC), postLOC (190 - 220 s after LOC). Statistical significance was determined with a repeated-measures ANOVA.ResultsLoss of consciousness was associated with an increase in the aperiodic exponent (young: p = 0.004, elderly: p = 0.007) and offset (young: p = 0.020, elderly: p = 0.004) as well as an increase in the adjusted power (young: p < 0.001, elderly p = 0.011) and center frequency (young: p = 0.008, elderly: p < 0.001) of the periodic alpha peak. We saw age-related differences in the aperiodic exponent and offset after LOC as well as in the power and bandwidth of the periodic alpha peak during LOC.ConclusionDecomposing the EEG spectrum over induction of anesthesia into its periodic and aperiodic components unveiled novel age-independent EEG markers of propofol-induced LOC: the aperiodic exponent and offset as well as the center frequency and adjusted power of the power peak in the alpha range.

Project description:Although the molecular effects of many anaesthetics have been well characterized, a network-level explanation for how these changes lead to loss of consciousness remains unclear. Studies using electroencephalography have characterized changes in neural oscillations in the cortex at specific frequency bands during propofol-induced anaesthesia and modelling work suggests these changes result from changes in thalamocortical functional connectivity. However, it is unclear if the neurophysiological changes seen at the cortex are due to enhanced or disrupted thalamocortical communication. Direct recordings from these sites during anaesthesia that could be used to confirm such models are rare. We recorded local field potentials from the ventral intermediate nucleus of the thalamus and electrocorticography signals from the ipsilateral sensorimotor cortex in 10 patients undergoing deep brain stimulation surgery. Signals were acquired during induction of propofol anaesthesia while subjects were resting. After confirming direct structural connectivity between the thalamus and the cortical recording site, we investigated propofol-associated changes in thalamic and cortical local power as well as thalamocortical functional connectivity, as measured with coherence, debiased weighted phase lag index, and phase amplitude coupling. Propofol anaesthesia resulted in local power increases at α frequencies (8-12 Hz) across both thalamic and cortical areas. At sensorimotor cortices, there was a broadband power increase (12-100 Hz), while the power of this same broad frequency band was suppressed within the thalamus. Despite the increase in local α power both within the thalamus and cortex, thalamocortical coherence and debiased weighted phase lag index in the α/low β frequencies (8-16 Hz, which was present in the awake state) significantly decreased with propofol administration (P < 0.05, two group test of coherence). Likewise, propofol administration resulted in decreased phase amplitude coupling between the phase of α/low β in the thalamus and the amplitude of broadband gamma (50-200 Hz) in the cortex (P = 0.031, Wilcoxon signed-rank test). We also report phase amplitude coupling between the phase of slow wave oscillations (0.1-1 Hz) and amplitude of broadband frequencies (8-200 Hz) within the cortex and across thalamocortical connections, during anaesthesia, both following a peak-max pattern. While confirming α-power increases with propofol administration both in thalamus and cortex, we observed decreased thalamocortical connectivity, contradicting models that suggest increasing cortical low frequency power is necessarily related to increased thalamocortical coherence but in support of the theory that propofol-induced loss of consciousness is associated with disrupted thalamocortical communication.

Dataset Information

The Impact of Age on Propofol Requirement for Inducing Loss of Consciousness in Elderly Surgical Patients.

Publications

The Impact of Age on Propofol Requirement for Inducing Loss of Consciousness in Elderly Surgical Patients.

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