Induction Phase Of Anesthesia Research Articles

Refractory Hypotension in Young Hypertension: A Case Report

With changes in lifestyle habits and reduced diagnostic thresholds for hypertension, the prevalence of hypertension among young individuals is expected to rise. We become aware of the adverse effects of pharmacological interventions related to anaesthesia. We present a case in which refractory hypotension emerged after the induction of anaesthesia for orthopaedic surgery. The procedure went smoothly, and there were no issues with the extubation in the intensive care unit. The patient required significantly more pharmacological support over an extended period of the procedure after developing refractory hypotension following an induction phase of anaesthesia that was resistant to fluid resuscitation. We present the case while addressing the current management and potential future management for a foreseeable future strategy.

Pharmacokinetic/Pharmacodynamic anesthesia model incorporating psi-Caputo fractional derivatives

We present a novel Pharmacokinetic/Pharmacodynamic (PK/PD) model for the induction phase of anesthesia, incorporating the ψ-Caputo fractional derivative. By employing the Picard iterative process, we derive a solution for a nonhomogeneous ψ-Caputo fractional system to characterize the dynamical behavior of the drugs distribution within a patient’s body during the anesthesia process. To explore the dynamics of the fractional anesthesia model, we perform numerical analysis on solutions involving various functions of ψ and fractional orders. All numerical simulations are conducted using the MATLAB computing environment. Our results suggest that the ψ functions and the fractional order of differentiation have an important role in the modeling of individual-specific characteristics, taking into account the complex interplay between drug concentration and its effect on the human body. This innovative model serves to advance the understanding of personalized drug responses during anesthesia, paving the way for more precise and tailored approaches to anesthetic drug administration.

An Analytic Method to Determine the Optimal Time for the Induction Phase of Anesthesia

We obtain an analytical solution for the time-optimal control problem in the induction phase of anesthesia. Our solution is shown to align numerically with the results obtained from the conventional shooting method. The induction phase of anesthesia relies on a pharmacokinetic/pharmacodynamic (PK/PD) model proposed by Bailey and Haddad in 2005 to regulate the infusion of propofol. In order to evaluate our approach and compare it with existing results in the literature, we examine a minimum-time problem for anesthetizing a patient. By applying the Pontryagin minimum principle, we introduce the shooting method as a means to solve the problem at hand. Additionally, we conducted numerical simulations using the MATLAB computing environment. We solve the time-optimal control problem using our newly proposed analytical method and discover that the optimal continuous infusion rate of the anesthetic and the minimum required time for transition from the awake state to an anesthetized state exhibit similarity between the two methods. However, the advantage of our new analytic method lies in its independence from unknown initial conditions for the adjoint variables.

Personalized asymmetric multiple PID to automatize the procedure of intravenous general anesthesia

General anesthesia has improved considerably over the years due to the automation of drug perfusion through closed-loop control which provided numerous advantages regarding efficiency and patient safety. This work describes the implementation and Validation of a control algorithm based on a multiple-input and multiple-output proportional–integral–derivative (MIMO-PID) controller. The main objective is to keep patients closer to the desired range of monitor values into satisfactory anesthetic state.The MIMO-PID decides the drug perfusion of propofol, remifentanil, and rocuronium based on the bispectral index, noxious stimulation response, and neuromuscular blockade monitorization. The main MIMO-PID variant is based on a feed-forward target which is used to define the asymmetric errors. The asymmetry allows different errors to be defined in each branch of each single-input and single-output proportional–integral–derivative. The MIMO-PID is tuned using the criterion of integral absolute error and their performance is evaluated through a range of experiments applying different metrics to evaluate monitors and drug perfusions. The satisfactory anesthetic state is achieved during the induction phase of anesthesia; however, we also had situations with a low relative deviation from the registered median values. We obtained good results by using a strict disturbance rejection.The controller was able to mitigate the surgery influence on the anesthetics effects when there were less than 20, the patient remained close to the desired anesthetic state. In the presence of significant or more numerous stimuli, the controller was able to achieve a satisfactory anesthetic state within a short period of typically less than 7 min.

The use of a scented face mask in pediatric patients may facilitate mask acceptance before anesthesia induction.

Scented face masks are commonly used during the induction phase of anesthesia. The present study investigated whether the use of a scented mask improved mask acceptance before the slow induction of anesthesia in pediatric patients. This prospective, randomized controlled trial enrolled patients aged 2-10 years who were scheduled to undergo surgery under general anesthesia. Patients were randomly assigned to either of regular unscented (control group) or scented (experimental group) face masks before anesthesia induction with a parent. The primary outcome was the mask acceptance score, rated on a validated 4-point from 1 point (not afraid; easily accepts the mask) to 4 points (afraid of a mask; crying or struggling). The secondary outcome was heart rate assessed by pulse oximetry in the pediatric ward before transfer to the operating room (OR), at the entrance to the OR, at the patient notification of mask fitting by the anesthesiologist, and after mask fitting. Seventy-seven patients were accessed for eligibility, with 67 enrolled in the study: 33 in the experimental group and 34 in the control group. Mask acceptance was significantly greater among patients aged 2-3 years in the experimental than in the control group (p < 0.05). The use of a scented mask can improve mask acceptance before anesthesia induction with a parental presence in pediatric patients aged 2-3 years.Clinical Trial Registration: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000040819.

Simulation-based Interprofessional Education (IPE) for Enhanced Attitude and Teamwork of Anesthesiology Residents and Nurse Anesthesia Students in Iran.

Simulation-based interprofessional education (IPE) provides the basis for the necessary competencies for interprofessional collaboration. This study aimed to examine the effects of this educational approach on anesthesia students' attitude and teamwork. This quasi-experimental study was performed on 72 anesthesiology residents and nurse anesthesia students consisting of 36 participants in the intervention and 36 in the control group. The intervention group participated in a simulation-based interprofessional season, including three scenarios in the induction phase of anesthesia. The control group received routine education. We used the Readiness for Interprofessional Learning Scale (RIPLS) to measure attitude and the KidSIM Team Performance Scale to assess teamwork. The data were analyzed by Analysis of Covariance, paired T-test, Chi-square, and Fischer's exact test in SPSS software, version 22. Comparing post-test scores by ANCOVA showed a significant difference between groups (p=0.001) because there was a significant positive change in the overall attitude score in the intervention group after receiving simulation-based IPE. Regarding the quality of teamwork, the intervention group's scores in all three sub-scales changed significantly after intervention (p<0.05). The simulation-based IPE is recommended to promote a teamwork culture and train empowered anesthesia professionals.

Intravenous Lidocaine for Postoperative Analgesia in 90 patients After Total Knee Arthroplasty and Limb Fractures.

BackgroundThe aim of this research was to investigate the analgesic effects of intravenous lidocaine on postoperative pain management in orthopedic patients after total joint arthroplasty and fractures of the limbs and to compare lidocaine efficacy between these orthopedic surgical procedures.Material/MethodsNinety patients scheduled for elective orthopedic surgery were recruited: 46 patients with total knee arthroplasty, and 35 patients with femoral fractures. Patients in the lidocaine group received lidocaine during the induction phase of anesthesia as a bolus injection of 1.5·kg−1·mg over 10 min, followed by intravenous infusion of 1.5 mg·kg−1·h−1 for 24 postoperative hours. Patients in the control group received an equal volume of saline as placebo administered at the same rate. Pain scores were assesed at intervals of 0, 15, 30, 60 min, and 6, 12, and 24 h postoperatively. The reduction rate of additional analgesics, total analgesic use, incidence of nausea and vomiting, mobilization, length of hospital stay, adverse effects, and hemodynamic parameters were secondary outcomes.ResultsPain scores at rest and during movement were significantly lower in the lidocaine group compared to those in controls starting at 30 min (P=0.03), the first postoperative hour, and also at 6, 12, and 24 h (P<0.001). Additional analgesics were administered at a significantly lower rate in the lidocaine group (P<0.05). Total analgesic use in the postoperative period was significantly higher in the control group (P<0.001).ConclusionsThis study showed that intravenous lidocaine provided adequate postoperative analgesia for orthopedic patients undergoing elective total joint arthroplasty and limb fracture repair.

Optimized feedforward control of propofol for induction of hypnosis in general anesthesia

ObjectiveWe propose the use of an optimization strategy for the determination of the initial propofol bolus for the induction phase of general anesthesia. MethodsThe optimized bolus minimizes the time-to-target and it is used as a feedforward action together with a specifically tuned PID feedback control system where the bispectral index is the controlled variable. ResultsA Monte Carlo method is used to verify the effectiveness of the proposed technique. Both intra-patient and inter-patient variability has been considered. A comparison with a control scheme based on a feedback PID controller only shows that the use of an optimized feedforward action allows an average reduction of the time-to-target of more than 25%, with an acceptable increment of the undershoot, which always remains above the BIS level of 30. ConclusionsThe use of an optimized bolus of propofol as a feedforward action in a fully automatic control system for the induction phase of anesthesia allows the anesthesiologist to reduce the transient time to obtain the required level of depth-of-hypnosis, without affecting the safety of the patient.

Impact of rapid versus gradual changes in arterial partial pressure of carbon dioxide on blood flow and myocardial oxygenation in an experimental anaesthetized model

Introduction Hyper- and hypocapnia have known vaso-modulatory effects in the coronary circulation. Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) detects changes in tissue oxygenation and can provide a comprehensive assessment of the impact of systemic blood gas changes on the myocardium. The purpose of this study was to compare the physiological responses to rapid blood gas changes induced by hyperventilation followed by apnea in comparison to steady-state levels of hypocapnia and hypercapnia in an experimental animal model. Methods Eighteen anaesthetized female swine were used in this study. A blood flow probe was attached to the left descending coronary artery (LAD) after a left-sided thoracotomy. In ten animals a hemodynamically significant LAD stenosis was induced, while eight animals served as controls. In a 3 Tesla MRI, paCO2 was modulated from a pre-set baseline (paO2=100mmHg/paCO2=40mmHg) to 30mmHg and subsequently 50mmHg by minor changes in ventilation rate. Rapid changes in paCO2 were achieved by 60s of hyperventilating (30/min) from baseline followed by an apnea of up to 90 seconds. OS-CMR images, coronary blood flow (CBF) of the LAD and arterial blood gases were recorded at each state. Results Targeting stable hypocapnia of 30mmHg from baseline did not alter CBF or myocardial oxygenation. Subsequent stable hypercapnia (paCO2=50mmHg) increased CBF significantly in control (5±5%, p=0.007) and stenosed (4±6%, p=0.036) animals, and myocardial oxygenation rose in both post-stenotic territories (4.2±6.2%, p=0.036) and in control subjects (6.2±6.2%, p=0.011). Rapid hyperventilation induced a similar degree of hypocapnia (control: paCO2=25±7mmHg, stenosed: 27±3mmHg) and showed a significant decrease of CBF by -34±23% (p=0.012) in healthy animals, and a significant decrease of -10±6% (p=0.010) in stenosed animals. This had no effect on tissue oxygenation. Apnea resulted in a similar paCO2 (control: paCO2=52±9mmHg, stenosed: 47±7mmHg) compared to steady-state blood gas levels, which increased CBF significantly in controls 346±327% (p=0.008) and stenosed 82±110 (p=0.039) animals markedly. By the end of apnea, a rise in tissue oxygenation of 2.9±2.2% was observed in controls (p=0.008), -2.7±5.1 (0.125) was observed in the stenosed group (Figure). Significant difference in myocardial oxygenation responses observed between control and stenosed subject was exclusively observed with apnea (p=0.011). Discussion Rapid hyperventilation followed by apnea results in more pronounced changes in myocardial blood flow than similar steady state deflections in paCO2. Only apnea after hyperventilation induced deoxygenation in the stenotic myocardium, which is in agreement with the concept of hypercapnia induced intercoronary steal, while steady state deviation did not compromise myocardial oxygenation. Similar breathing maneuvers may be seen in the induction phase of anaesthesia, which could potentially be a harbinger of perioperative ischemic myocardial events.

The Performance of an Artificial Neural Network Model in Predicting the Early Distribution Kinetics of Propofol in Morbidly Obese and Lean Subjects.

Induction of anesthesia is a phase characterized by rapid changes in both drug concentration and drug effect. Conventional mammillary compartmental models are limited in their ability to accurately describe the early drug distribution kinetics. Recirculatory models have been used to account for intravascular mixing after drug administration. However, these models themselves may be prone to misspecification. Artificial neural networks offer an advantage in that they are flexible and not limited to a specific structure and, therefore, may be superior in modeling complex nonlinear systems. They have been used successfully in the past to model steady-state or near steady-state kinetics, but never have they been used to model induction-phase kinetics using a high-resolution pharmacokinetic dataset. This study is the first to use an artificial neural network to model early- and late-phase kinetics of a drug. Twenty morbidly obese and 10 lean subjects were each administered propofol for induction of anesthesia at a rate of 100 mg/kg/h based on lean body weight and total body weight for obese and lean subjects, respectively. High-resolution plasma samples were collected during the induction phase of anesthesia, with the last sample taken at 16 hours after propofol administration for a total of 47 samples per subject. Traditional mammillary compartment models, recirculatory models, and a gated recurrent unit neural network were constructed to model the propofol pharmacokinetics. Model performance was compared. A 4-compartment model, a recirculatory model, and a gated recurrent unit neural network were assessed. The final recirculatory model (mean prediction error: 0.348; mean square error: 23.92) and gated recurrent unit neural network that incorporated ensemble learning (mean prediction error: 0.161; mean square error: 20.83) had similar performance. Each of these models overpredicted propofol concentrations during the induction and elimination phases. Both models had superior performance compared to the 4-compartment model (mean prediction error: 0.108; mean square error: 31.61), which suffered from overprediction bias during the first 5 minutes followed by under-prediction bias after 5 minutes. A recirculatory model and gated recurrent unit artificial neural network that incorporated ensemble learning both had similar performance and were both superior to a compartmental model in describing our high-resolution pharmacokinetic data of propofol. The potential of neural networks in pharmacokinetic modeling is encouraging but may be limited by the amount of training data available for these models.

Prediction of Blood Pressure after Induction of Anesthesia Using Deep Learning: A Feasibility Study

Anesthesia induction is associated with frequent blood pressure fluctuation such as hypotension and hypertension. If it is possible to precisely predict blood pressure a few minutes ahead, anesthesiologists can proactively give anesthetic management before patients develop hemodynamic problem. The objective of this study is to develop a real-time model for predicting 3-min-ahead blood pressure from the start of anesthesia induction to surgical incision. We used only vital signs and anesthesia-related data obtained during anesthesia-induction phase and designed a bidirectional recurrent neural network followed by fully connected layers. We conducted experiments on our collected data of 102 patients, and obtained mean absolute errors between 8.2 mmHg and 11.1 mmHg and standard deviation between 8.7 mmHg and 12.7 mmHg. The average elapsed time for prediction of a batch of 100 unseen data was about 26.56 milliseconds. We believe that this study shows feasibility of real-time prediction of future blood pressures, and the performance will be improved by collecting more data and finding better model structures.

Time-optimal control for the induction phase of anesthesia

This paper deals with the control of the induction phase of anesthesia. The objective during this first phase is to bring the patient from its awake state to a final state corresponding to some given depth of anesthesia, measured by the BIS (Bispectral index), within a minimum time. This optimal time control strategy is addressed by means of the maximum principle of Pontryagin. Furthermore, since the anesthesia model presents multiple time scale dynamics that can be split in two groups : fast and slow and since the BIS is a direct function of the fast ones, we only consider the optimal control of fast states. The final state of the slow dynamics is let free. The synthesis approach of the optimal control is detailed then tested in the case of a nominal patient.

Riboflavin-responsive ACAD9 mutation as cause of familial hypertrophic cardiomyopathy

Case description: A 9 months old male infant suffered from cardiorespiratory failure during the induction phase of anaesthesia for correction of umbilical hernia. Although it was first possible to stabilise him, he was found to have an underlying hypertrophic cardiomyopathy with severe lactic acidosis in serum. He developed brain oedema and died at the intensive care unit. Methods & Results: A biopsy was taken from heart, skeletal muscle and liver to perform OXPHOS measurements and BN-PAGE which showed isolated complex I deficiency in all the tissues. Because he was part of a twin (binovular), his brother also underwent an echocardiogram which likewise showed hypertrophic cardiomyopathy. Extensive metabolic work-up was done. The profile of the amino acids and sialotransferrins was normal and Pompe disease was excluded. The profile of the urinary organic acids and acylcarnitines showed the presence of severe lactic acidosis and ketosis. As mtDNA research was negative, extensive genetic search was started. In the meanwhile, the mother gave birth to another twin. The girl was normal but the male suffered from hypertrophic cardiomyopathy and increased lactate concentrations. When compared to the sister, it was striking that they were more passive and much easier tired. They also regularly felt when walking. As therapy, both affected siblings received atenolol and vitamin B2 (3 × 10 mg/day). A compound heterozygote mutation was found for c.868G>A (p.Gly290Arg) and c.1237G>A (p.Glu413Lys), causing ACAD9 deficiency. The dose of riboflavin was increased to 100 mg/day. From that moment, there was significant improvement of their cognitive and motor functioning. Conclusion: Acting as assembly factor for complex I, ACAD9 deficiency can cause isolated complex I deficiency. It is suggested that ACAD9 mutations impair folding, resulting in a more difficult binding of fatty acids and FAD. In this perspective, riboflavin supplementation may increase ACAD9 activity and stability, causing clinical improvement.

Refining Target-Controlled Infusion: An Assessment of Pharmacodynamic Target-Controlled Infusion of Propofol and Remifentanil Using a Response Surface Model of Their Combined Effects on Bispectral Index.

Propofol and remifentanil are commonly combined for total IV anesthesia. The pharmacokinetics (PK), pharmacodynamics (PD), and drug interactions of the combination are well understood, but the use of a combined PK and PD model to control target-controlled infusion pumps has not been investigated. In this study, we prospectively tested the accuracy of a PD target-controlled infusion algorithm for propofol and remifentanil using a response surface model of their combined effects on Bispectral Index (BIS). Effect-site, target-controlled infusions of propofol and remifentanil were given using an algorithm based on standard PK models linked to a PD response surface model of their combined effects on BIS. The combination of a targeted BIS value and adjustable ratio of propofol to remifentanil was used to adjust infusion rates. The standard model performance measures of median performance error (bias) and median absolute performance error (inaccuracy), expressed as percentages, were used to assess accuracy of the infusions in a convenience sample of 50 adult patients undergoing surgery with general anesthesia. The influence of age and weight on the performance of the model was also assessed. Patients had a mean (range) age of 48 (19-73) years, weight of 80 (45-169) kg, and body mass index of 28 (19-45) kg/m. The overall model had a bias of 8% (SD 24%) and inaccuracy of 25% (SD 13%). Performance was least accurate during the early induction phase of anesthesia. There was no significant bias in BIS predictions with increasing age (P = 0.44) or weight (P = 0.56). The algorithm performed adequately in a clinical setting. The algorithm could be further refined, and assessment of its accuracy and utility in comparison to current clinical practice for giving IV anesthesia is warranted.

Intraperitoneal co-administration of low dose urethane with xylazine and ketamine for extended duration of surgical anesthesia in rats

Procedures involving complex surgical techniques in rats, such as placement of abdominal aortic graft require extended duration of surgical anesthesia, which often can be achieved by repeated administrations of xylazine-ketamine combination. However such repeated anesthetic administration, in addition to being technically challenging, may be associated with potential adverse events due to cumulative effects of anesthesia. We report here the feasibility of using urethane at low dose (~1/10 the recommended anesthetic dose) in combination with a xylazine-ketamine mix to achieve an extended duration of surgical anesthesia in rats. The anesthesia induction phase was quick and smooth with an optimal phase of surgical anesthesia achieved for up to 90 minutes, which was significantly higher compared to that achieved with use of only xylazine-ketamine combination. The rectal temperature, heart rate and respiratory rate were within the physiological range with an uneventful recovery phase. Post surgery the rats were followed up to 3 months without any evidence of tumor or any other adverse effects related to the use of the urethane anesthetic combination. We conclude that low dose urethane can be effectively used in combination with xylazine and ketamine to achieve extended duration of surgical anesthesia up to 90 minutes in rats.

Prospective Pilot Investigation: Presurgical Depressive Symptom Severity and Anesthesia Response in Women Undergoing Surgery for Gynecologic Mass Removal.

Anesthesia depth has been associated with mortality. The association between anesthesia depth and presurgery physical and health status, however, is currently debated. Depression is one comorbid condition that warrants investigation given its association to reduced frontal lobe activity and high prevalence in known surgery samples (e.g., gynecologic mass removal). This pilot study examined the hypothesis that severity of acute depressive symptoms would associate with greater sensitivity to anesthesia as measured by a frontal lobe electroencephalogram (EEG)-based monitor during the anesthesia induction phase among women undergoing gynecologic mass removal. This was a prospective and surgery anesthesia-controlled pilot investigation with 31 women undergoing surgery for removal of pelvic/gynecologic masses. Participants completed the Millon Behavioral Medicine Diagnostic (MBMD) inventory to assess depressive-related symptomatology. A Bispectral Index Score (BIS™) monitor (Aspect Medical Systems Inc., MA) was placed on the left frontal region to measure change in response from a set pre-anesthesia baseline point throughout the induction phase (6.5 min of the anesthetic). BIS™ change was calculated using a modified "area under the curve with respect to ground" formula. Greater sensitivity to anesthesia during induction was significantly associated with higher MBMD future pessimism scores and marginally associated with higher MBMD depression scores. Depressive personality, anxiety severity, tumor type, age, medication use, and comorbidity scores were not found to be predictors of BIS score change. These pilot findings suggest that preoperative psychological health and anesthesia response are not independent. Acute presurgery depression and anesthesia response warrant closer empirical examination.

Antibiotics Are an Important Identifiable Cause of Perioperative Anaphylaxis in the United States

The diagnosis of perioperative anaphylaxis (PA) remains challenging, given its clinical setting, exposure to multiple medications, and rarity. Previous reports have found that PA is most frequently caused by neuromuscular-blocking agents. To determine characteristics and causes of PA at our center. We performed a retrospective medical record review to identify patients with anaphylaxis. Cases were further categorized by manifestations of anaphylaxis, age, sex, atopy, timing, tryptase level, and previous PA events. Cases with a cause identified by skin or in vitro tests were classified as IgE-mediated anaphylaxis. Thirty cases were identified. Seventeen (57%) had an identifiable cause: antibiotics in 10 (59%)-β-lactams in and metronidazole in 1; latex in 3 (18%); and neuromuscular blockers in 4 (23%). There was no identifiable cause in 13 cases. The most frequent presenting sign of PA was hypotension (97%). Seven patients (23%) presented with cardiac arrest. A minority (17%) exhibited urticaria. Only four had a history of atopy. Most of the reactions occurred during the anesthesia induction phase. Elevated serum tryptase level was found in 10 of 10 (100%) cases of IgE-mediated anaphylaxis compared with 4 of 10 (40%) cases without an identifiable cause. We found that antibiotics were the most common identifiable cause of PA. Our findings imply that antibiotic exposure warrants careful attention in the evaluation and management of patients with PA, particularly for those who require repeat and/or future surgeries.

Does pharmacotherapy influence the inflammatory responses during cardiopulmonary bypass in children?

Cardiopulmonary bypass (CPB) induces a systemic inflammatory response syndrome (SIRS) by factors such as contact of the blood with the foreign surface of the extracorporeal circuit, hypothermia, reduction of pulmonary blood flow during CPB and endotoxemia. SIRS is maintained in the postoperative phase, co-occurring with a counter anti-inflammatory response syndrome. Research on the effects of drugs administered before the surgery, especially in the induction phase of anesthesia, as well as drugs used during extracorporeal circulation, has revealed that they greatly influence these postoperative inflammatory responses. A better understanding of these processes may not only improve postoperative recovery but also enable tailor-made pharmacotherapy, with both health and economic benefits. In this review, we describe the pathophysiology of SIRS and counter anti-inflammatory response syndrome in the light of CPB in children and the influence of drugs used on these syndromes.

GABAergic transmission in rat pontine reticular formation regulates the induction phase of anesthesia and modulates hyperalgesia caused by sleep deprivation

The oral part of the pontine reticular formation (PnO) contributes to the regulation of sleep, anesthesia and pain. The role of PnO γ-aminobutyric acid (GABA) in modulating these states remains incompletely understood. The present study used time to loss and time to resumption of righting response (LoRR and RoRR) as surrogate measures of loss and resumption of consciousness. This study tested three hypotheses: (i) pharmacologically manipulating GABA levels in rat PnO alters LoRR, RoRR and nociception; (ii) propofol decreases GABA levels in the PnO; and (iii) inhibiting GABA synthesis in the PnO blocks hyperalgesia caused by sleep deprivation. Administering a GABA synthesis inhibitor [3-mercaptopropionic acid (3-MPA)] or a GABA uptake inhibitor [nipecotic acid (NPA)] into rat PnO significantly altered LoRR caused by propofol. 3-MPA significantly decreased LoRR for propofol (-18%). NPA significantly increased LoRR during administration of propofol (36%). Neither 3-MPA nor NPA altered RoRR following cessation of propofol or isoflurane delivery. The finding that LoRR was decreased by 3-MPA and increased by NPA is consistent with measures showing that extracellular GABA levels in the PnO were decreased (41%) by propofol. Thermal nociception was significantly decreased by 3-MPA and increased by NPA, and 3-MPA blocked the hyperalgesia caused by sleep deprivation. The results demonstrate that GABA levels in the PnO regulate the time for loss of consciousness caused by propofol, extend the concept that anesthetic induction and emergence are not inverse processes, and suggest that GABAergic transmission in the PnO mediates hyperalgesia caused by sleep loss.

Individualized closed-loop control of propofol anesthesia: A preliminary study

This paper proposes an individualized approach to closed-loop control of depth of hypnosis during propofol anesthesia. The novelty of the paper lies in the individualization of the controller at the end of the induction phase of anesthesia, based on a patient model identified from the dose–response relationship during induction of anesthesia. The proposed approach is shown to be superior to administration of propofol based on population-based infusion schemes tailored to individual patients. This approach has the potential to outperform fully adaptive approaches in regards to controller robustness against measurement variability due to surgical stimulation. To streamline controller synthesis, two output filters were introduced (inverting the Hill dose–response model and the linear time-invariant sensor model), which yield a close-to-linear representation of the system dynamics when used with a compartmental patient model. These filters are especially useful during the induction phase of anesthesia in which a nonlinear dose–response relationship complicates the design of an appropriate controller. The proposed approach was evaluated in simulation on pharmacokinetic and pharmacodynamic models of 44 patients identified from real clinical data. A model of the NeuroSense, a hypnotic depth monitor based on wavelet analysis of EEG, was also included. This monitor is similar to the well-known BIS, but has linear time-invariant dynamics and does not introduce a delay. The proposed scheme was compared with a population-based controller, i.e. a controller only utilizing models based on demographic covariates for its tuning. On average, the proposed approach offered 25% improvement in disturbance attenuation, measured as the integrated absolute error following a step disturbance. The corresponding standard deviation from the reference was also decreased by 25%. Results are discussed and possible directions of future work are proposed.