An exploratory study of the relationship between postoperative nausea and vomiting and postdischarge nausea and vomiting in children undergoing ambulatory surgery.

BACKGROUND: The factors contributing to postoperative nausea and vomiting in children have been identified, but there have been no reported studies that have studied pediatric postdischarge nausea and vomiting. AIMS: This preliminary study aimed to identify  the factors affecting postdischarge nausea and vomiting in ambulatory children, specifically whether postoperative nausea and vomiting factors are contributory. METHODS: One hundred and twenty-two pediatric patients aged 5-10 years undergoing elective ambulatory surgery participated in this institution-approved study. After obtaining written parental consent and patient assent when indicated, child self-ratings of nausea and pain were completed preoperatively and at discharge, and for 3 days postdischarge. Questionnaires were returned by mail, with a 64% return rate. Using stepwise logistic regression with backward elimination, three separate analyses were undertaken to predict the following outcomes: nausea present in recovery, nausea present on postoperative day 1, and emesis on day of surgery. RESULTS: Nearly half (47%) of our cohort experienced nausea at the time of discharge; 11% had emesis on day of surgery. On postoperative day 1, there was a 15% incidence of nausea with a 3% incidence of emesis. In the multiple logistic regression analyses, nausea at discharge was predicted by male gender (odds ratio 2.5, 95% CI: 1.0-6.2) and the presence of pain on discharge (odds ratio 3.0, 95% CI: 1.0-9.2). Emesis on day of surgery was predicted by the presence of nausea at discharge (odds ratio 16.9, 95% CI: 1.8-159.3) and having a family history of nausea/vomiting (odds ratio 8.3, 95% CI: 1.6-43.4). The presence of nausea on postoperative day 1 was predicted only by the presence of nausea on discharge (odds ratio 3.7, 95% CI: 1.2-11.1). CONCLUSION: Our preliminary data indicate that postoperative nausea and vomiting may persist into the postdischarge period and pain may be a contributing factor.

Sleep problems in breast cancer survivors 1-10 years posttreatment.

ABSTRACTObjective:Sleep can affect quality of life (QoL) during cancer survivorship, and symptoms related to poor sleep can be exacerbated. We examined the prevalence, severity, and nature of subjective sleep complaints in women surviving stage I-III breast cancer who were 1-10 years posttreatment. We also examined the demographic, medical, physical, and psychosocial correlates of poor sleep in these women in order to identify the subgroups that may be most in need of intervention. METHOD: A total of 200 patients at a comprehensive cancer center who were 1-10 years posttreatment for primary stage I-III breast cancer with no evidence of disease at the time of enrollment completed a battery of questionnaires on demographics, sleep, physical symptoms, mood, cancer-specific fears, and QoL. RESULTS: The women had a mean age of 57 years (SD = 10.0), with a mean of 63.3 months (SD = 28.8) of post-cancer treatment. Some 38% of these patients were identified as having poor-quality sleep. Women with poor sleep took longer to fall asleep, had more awakenings, and acquired 2 hours less sleep per night than those with good sleep. They also had a lower QoL, greater severity of pain, more concerns about health and recurrence, and increased vasomotor symptoms (p < 0.05). Daytime sleepiness and depression were found to be not significantly correlated with sleep quality. SIGNIFICANCE OF RESULTS: Many breast cancer survivors had severe subjective insomnia, and several breast cancer survivor subgroups were identified as having members who might be most in need of sleep-improvement interventions. Addressing physical symptoms (e.g., vasomotor symptoms and pain) and providing education about the behavioral, social, environmental, and medical factors that affect sleep could result in substantial improvement in the life course of breast cancer survivors.

Visual P2-N2 complex and arousal at the time of encoding predict the time domain characteristics of amnesia for multiple intravenous anesthetic drugs in humans.

BACKGROUND: Intravenous anesthetics have marked effects on memory function, even at subclinical concentrations. Fundamental questions remain in characterizing anesthetic amnesia and identifying affected system-level processes. The authors applied a mathematical model to evaluate time-domain components of anesthetic amnesia in human subjects. METHODS: Sixty-one volunteers were randomized to receive propofol (n = 12), thiopental (n = 13), midazolam (n = 12), dexmedetomidine (n = 12), or placebo (n = 12). With drug present, subjects encoded pictures into memory using a 375-item continuous recognition task, with subsequent recognition later probed with drug absent. Memory function was sampled at up to 163 time points and modeled over the time domain using a two-parameter, first-order negative power function. The parietal event-related P2-N2 complex was derived from electroencephalography, and arousal was repeatedly sampled. Each drug was evaluated at two concentrations. RESULTS: The negative power function consistently described the course of amnesia (mean R = 0.854), but there were marked differences between drugs in the modulation of individual components (P < 0.0001). Initial memory strength was a function of arousal (P = 0.005), whereas subsequent decay was related to the reaction time (P < 0.0001) and the P2-N2 complex (P = 0.007/0.002 for discrete components). CONCLUSIONS: In humans, the amnesia caused by multiple intravenous anesthetic drugs is characterized by arousal-related effects on initial trace strength, and a subsequent decay predicted by attenuation of the P2-N2 complex at encoding. The authors propose that the failure of normal memory consolidation follows drug-induced disruption of interregional synchrony critical for neuronal plasticity and discuss their findings in the framework of memory systems theory.

Evaluating the utility of fasting lipid panel in addition to random lipid panel in determining lipid-lowering therapy in acute ischemic stroke or TIA patients.

BACKGROUND: Hyperlipidemia is one of the major risk factors for cerebrovascular disease and it is common practice to obtain fasting lipid profile prior to starting lipid lowering therapy (LLT). Recent AHA Guidelines published in 2018 allow for a non-fasting value to be used. OBJECTIVE: To determine if obtaining fasting lipid levels in addition to random lipid levels prompts changes in hyperlipidemia management of acute stroke patients. METHODS: 206 patients met the study criteria which included a diagnosis of acute ischemic stroke or transient ischemic attack on admission and availability of both random and fasting LDL levels collected within 72 h of each other. Patients were divided into three groups based on random LDL at admission: Group A: LDL < 70, Group B: LDL 70-99, and Group C: LDL ≥ 100 mg/dL. The dataset was analyzed to conform to the 2018 AHA/ACC guidelines using an LDL cutoff of 70 mg/dL. RESULTS: In 206 patients, statin management would change based on the fasting LDL level in 12 patients, 11 of whom were in Group B. Our data suggests that lipid management is more likely to change if the initial random LDL falls between 70-99 mg/dL as compared to a value outside of this range (P < 0.001). We present a decision algorithm to guide lipid management in acute stroke patients. CONCLUSIONS: Foregoing a fasting lipid panel to guide LLT in patients with ischemic stroke is appropriate in most cases but for select patients with random LDL levels between 70 and 99, fasting lipid profile should be obtained prior to deciding upon LLT.

Propofol and midazolam inhibit conscious memory processes very soon after encoding: an event-related potential study of familiarity and recollection in volunteers.

BACKGROUND: Intravenous drugs active via gamma-aminobutyric acid receptors to produce memory impairment during conscious sedation. Memory function was assessed using event-related potentials (ERPs) while drug was present. METHODS: The continuous recognition task measured recognition of photographs from working (6 s) and long-term (27 s) memory while ERPs were recorded from Cz (familiarity recognition) and Pz electrodes (recollection recognition). Volunteer participants received sequential doses of one of placebo (n = 11), 0.45 and 0.9 microg/ml propofol (n = 10), 20 and 40 ng/ml midazolam (n = 12), 1.5 and 3 microg/ml thiopental (n = 11), or 0.25 and 0.4 ng/ml dexmedetomidine (n = 11). End-of-day yes/no recognition 225 min after the end of drug infusion tested memory retention of pictures encoded on the continuous recognition tasks. RESULTS: Active drugs increased reaction times and impaired memory on the continuous recognition task equally, except for a greater effect of midazolam (P < 0.04). Forgetting from continuous recognition tasks to end of day was similar for all drugs (P = 0.40), greater than placebo (P < 0.001). Propofol and midazolam decreased the area between first presentation (new) and recognized (old, 27 s later) ERP waveforms from long-term memory for familiarity (P = 0.03) and possibly for recollection processes (P = 0.12). Propofol shifted ERP amplitudes to smaller voltages (P < 0.002). Dexmedetomidine may have impaired familiarity more than recollection processes (P = 0.10). Thiopental had no effect on ERPs. CONCLUSION: Propofol and midazolam impaired recognition ERPs from long-term memory but not working memory. ERP measures of memory revealed different pathways to end-of-day memory loss as early as 27 s after encoding.

Transcutaneous CO2 versus end-tidal CO2 in neonates and infants undergoing surgery: a prospective study.

Aim: End-tidal CO2 (EtCO2) is the standard in operative care along with pulse oximetry for ventilation assessment. It is known to be less accurate in the infant population than in adults. Many neonatal intensive care units (NICU) have converted to utilizing transcutaneous CO2 (tcPCO2) monitoring. This study aimed to compare perioperative EtCO2 to tcPCO2 in the pediatric perioperative population specifically below 10 kg, which encompasses neonates and some infants. Methods: After IRB approval and parental written informed consent, we enrolled neonates and infants weighing less than 10 kg, who were scheduled for elective surgery with endotracheal tube under general anesthesia. PCO2 was monitored with EtCO2 and with tcPCO2. Venous blood gas (PvCO2) samples were drawn at the end of the anesthetic. We calculated a mean difference of EtCO2 minus PvCO2 (Delta EtCO2), and tcPCO2 minus PvCO2 (Delta tcPCO2) from end-of-case measurements. The mean differences in the NICU and non-NICU patients were compared by t-tests and Bland-Altman analysis. Results: Median age was 10.9 weeks, and median weight was 4.4 kg. NICU (n=6) and non-NICU (n=14) patients did not differ in PvCO2. Relative to the PvCO2, the Delta EtCO2 was much greater in the NICU compared to the non-NICU patients (-28.1 versus -9.8, t=3.912, 18 df, P=0.001). Delta tcPCO2 was close to zero in both groups. Although both measures obtained simultaneously in the same patients agreed moderately with each other (r =0.444, 18 df, P=0.05), Bland-Altman plots indicated that the mean difference (bias) in EtCO2 measurements differed significantly from zero (P<0.05). Conclusions: EtCO2 underestimates PvCO2 values in neonates and infants under general anesthesia. TcPCO2 closely approximates venous blood gas values, in both the NICU and non-NICU samples. We, therefore, conclude that tcPCO2 is a more accurate measure of operative PvCO2 in infants, especially in NICU patients.

Low-dose propofol-induced amnesia is not due to a failure of encoding: left inferior prefrontal cortex is still active.

BACKGROUND: Propofol may produce amnesia by affecting encoding. The hypothesis that propofol weakens encoding was tested by measuring regional cerebral blood flow during verbal encoding. METHODS: Seventeen volunteer participants (12 men; aged 30.4 +/- 6.5 yr) had regional cerebral blood flow measured using H2O positron emission tomography during complex and simple encoding tasks (deep vs. shallow level of processing) to identify a region of interest in the left inferior prefrontal cortex (LIPFC). The effect of either propofol (n = 6, 0.9 microg/ml target concentration), placebo with a divided attention task (n = 5), or thiopental at sedative doses (n = 6, 3 microg/ml) on regional cerebral blood flow activation in the LIPFC was tested. The divided attention task was expected to decrease activation in the LIPFC. RESULTS: Propofol did not impair encoding performance or reaction times, but impaired recognition memory of deeply encoded words 4 h later (median recognition of 35% [interquartile range, 17-54%] of words presented during propofol vs. 65% [38-91%] before drug; P < 0.05). Statistical parametric mapping analysis identified a region of interest of 6.6 cm in the LIPFC (T = 7.44, P = 0.014). Regional cerebral blood flow response to deep encoding was present in this region of interest in each group before drug (T > 4.41, P < 0.04). During drug infusion, only the propofol group continued to have borderline significant activation in this region (T = 4.00, P = 0.063). CONCLUSIONS: If the amnesic effect of propofol were solely due to effects on encoding, activation in the LIPFC should be minimal. Because LIPFC activation was not totally eliminated by propofol, the amnesic action of propofol must be present in other brain regions and/or affect other memory processes.

Interleukin-6 and leptin levels are associated with preoperative pain severity in patients with osteoarthritis but not with acute pain after total knee arthroplasty.

BACKGROUND: Identifying drivers of pain that can serve as novel drug targets is important for improving perioperative analgesia. Total knee arthroplasty (TKA) is associated with significant postoperative pain. Cytokines contribute to the pathophysiology of osteoarthritis (OA) and associated pain. However, the influence of perioperative cytokine levels after TKA surgery upon postoperative pain remains unexplored. METHODS: We designed a prospective observational study to profile three proinflammatory cytokines, interleukin-6 (IL-6), tumor necrosis factor α (TNFα), and leptin in serum, synovial, and cerebrospinal fluid of TKA patients perioperatively to determine associations between cytokine levels and pain. We characterized time-trajectories in cytokines pre- and post-surgery and explored their relationships to pain across gender. RESULTS: Preoperative pain, measured by functional pain disability scores (PDQ), was predictive of postoperative pain. There were no gender differences in severity of preoperative pain or acute postoperative pain. Serum IL-6, serum leptin, and synovial fluid leptin were positively correlated with body mass index and preoperative pain severity. Stratification of patients by gender revealed strong correlations between serum IL-6, leptin, and PDQ only in females, suggesting that females may be more sensitive to the nociceptive actions of these cytokines. Although serum IL-6 increased dramatically (and TNFα increased modestly) four hours after surgery and remained elevated at 72h; they were not associated with the severity of acute postoperative pain. CONCLUSIONS: Our data suggest that while preoperative chronic pain is predictive of the severity of acute postoperative pain in TKA patients, the pre- and post-operative inflammatory status does not predict postoperative pain.

Polysomnographic Study of Sleep in Survivors of Breast Cancer.

STUDY OBJECTIVE: Insomnia is a frequent complaint in breast cancer patients during and after treatment. Breast cancer survivors, 1-10 years posttreatment, underwent in-lab polysomnography (PSG) to objectively define the insomnia in those patients with such a complaint. METHODS: Twenty-six breast cancer survivors (aged 39-80, mean 54.0 months posttreatment) spent 2 nights in the sleep laboratory. Sleep on Night 2 was scored for sleep stages, sleep onset latency, REM sleep onset latency, wake time, apneas and hypopneas, periodic limb movements and arousals. Subjects were allocated into 2 groups by their scores on the Pittsburgh Sleep Quality Index (PSQI): no/ mild sleep disturbance (PSQI score ≤ 9, n = 15) or moderate/ severe sleep disturbance (PSQI ≥ 10, n = 11). RESULTS: Standard PSG/EEG parameters failed to differentiate insomniacs from non-insomniacs. The single variable that distinguished the insomnia group was periodic limb movements in sleep (PLMS). PLMS were significantly correlated (r ≅ 0.7, p < 0.02) with subjective report of insomnia on PSQI and insomnia severity index. Log[Number of PLMS] was higher in the moderate/severe insomnia group (p = 0.008). Five of 11 patients in the moderate/severe insomnia group had a PLMS index ≥ 15, compared to only one of 15 patients in the none/mild insomnia group (p = 0.02). Menopausal symptoms and use of caffeine, hypnotics, and antidepressants were unrelated to insomnia severity or PLMS. CONCLUSIONS: PLMS was the sole PSG variable that separated breast cancer survivors with moderate/severe insomnia from those with no/mild sleep disturbance. Further study of the incidence and significance of PLMS in breast cancer survivors with the complaint of insomnia is merited.

Midazolam decreases cerebral blood flow in the left prefrontal cortex in a dose-dependent fashion.

Midazolam, a short-lived benzodiazepine producing sedation and reversible anterograde amnesia, was administered intravenously to 14 healthy male volunteers. Regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with intravenous H2 15O at either a 'high' midazolam EEG effect (EEG signs of stage 2 sleep), or 'low' midazolam EEG effect (increase in EEG beta power only). Memory tests administered following PET scans showed significant drug-induced impairment in learning and retrieval at the same drug concentration at which PET images were acquired. Statistical parametric mapping was used to identify regions where rCBF changes after drug administration were significantly different in the high- vs. low- effect groups. Dosexcondition interactions were found in the left dorsolateral prefrontal cortex [Brodmann's areas (BA) 9 and 46], bilateral orbital-frontal cortex (BA 47), the left middle temporal gyrus (BA 22) and the right hippocampus. The predominantly left frontal rCBF decreases occur in a region associated with semantic processing, working memory, and encoding of verbal material, a process preferentially affected by midazolam. Our interpretation is that rCBF changes in the hippocampus are unlikely to mediate the anterograde amnesia produced by midazolam. Although in the present study PET images were acquired during the resting state rather than during memory processing, these results underscore the need for further investigation relating to the interaction of midazolam with specific cognitive operations in these brain regions.

A survey on teaching ultrasound-guided chronic pain procedures in pain medicine fellowship programs.

BACKGROUND: Over the last decade ultrasound guidance (USG) has been utilized very successfully in acute pain procedures to confirm nerves' anatomic location and obtain live images. Not only the utilization, but the teaching, of USG has become an essential part of anesthesiology residency training. Prior to the introduction of USG, chronic pain procedures were always done either under fluoroscopy or blindly. USG offers advantages over fluoroscopy for completion of chronic pain procedures. USG decreases radiation exposure and the expenses associated with operating a fluoroscopy machine and allows live visualization of soft tissues and blood flow, a feature that fluoroscopy does not directly offer. Even today, the utilization and teaching of the technique for chronic pain procedures has not been as widely accepted as in acute pain management. OBJECTIVES: To understand the current practices and the factors affecting the teaching of ultrasound guided chronic pain procedures in chronic pain fellowship programs throughout the United States. STUDY DESIGN: Survey conducted by internet and mail. The survey was distributed to program directors of ACGME-accredited pain medicine fellowships. When the survey was distributed there were 92 accredited pain medicine fellowships. METHODS: REDCap survey software was used for designing the questionnaire and sending email invitations. Also, paper questionnaires were sent to those who did not respond electronically. Additional copies of the survey were mailed or faxed upon request. We received 43 responses (a response rate of 46.7%). Statistical analyses included frequencies, crosstabs, and nonparametric Spearman rank-order correlations. RESULTS: The majority of stellate ganglion blocks, occipital nerve blocks, and peripheral nerve blocks are currently being done under ultrasound guidance. Although interest among trainees is very high, only 48.8% of the fellowship programs require fellows to learn the technique before graduation and 32.6% of the program directors agree that teaching of USG should be an ACGME requirement for pain medicine fellowship training. Faculty training is considered to be the most important factor for teaching the technique by 62.8% of directors. In the opinion of the majority of program directors, the greatest factor that stands against teaching the technique is the fact that it is time consuming. Nearly half (44.2%) of program directors believe that the technique will never replace fluoroscopy; but one quarter (25.6%) think that the new 3D ultrasound technology, when available, will replace fluoroscopy. LIMITATIONS: A moderate response rate (46.7%) may limit the generalizability of the findings. However, our survey respondents seem to represent the study population quite well, although there was a bias towards the university-based programs. Training programs located at community-based hospitals and U.S. government installations were not as well represented. CONCLUSION: The teaching of ultrasound guided chronic pain procedures varies significantly between individual programs. Though many program directors do require that fellows demonstrate competency in the technique before graduation, as of today there is no ACGME guideline regarding this. The advancement in ultrasound technology and the increase in number of trained faculty may significantly impact the use of USG in training fellows to perform chronic pain procedures.

Brain metabolomic profiles of lung cancer patients prior to treatment characterized by proton magnetic resonance spectroscopy.

Cancer patients without evidence of brain metastases often exhibit constitutional symptoms, cognitive dysfunction and mood changes at the time of clinical diagnosis, i.e. prior to surgical and/or chemotherapy treatment. At present however, there is limited information on brain metabolic and functional status in patients with systemic cancers such as lung cancer prior to initiation of treatment. Therefore, a prospective, observational study was conducted on patients with a clinical diagnosis of lung cancer to assess the cerebral metabolic status before treatment using proton magnetic resonance spectroscopy ((1)HMRS). Together with neurocognitive testing, (1)HMRS was performed in the parietal and occipital cortices of patients diagnosed with a lung mass (N=17) and an age-matched control group (N=15). Glutamate concentrations in the occipital cortex were found to be lower in the patients compared to controls and the concentrations of creatine and phosphocreatine were significantly lower in the parietal cortex of the patients. The lung cancer patients were also characterized by greater fatigue scores (but not depression) prior to treatment when compared to controls. In addition, the serum concentration of interleukin-6 (proinflammatory cytokine) was higher in patients compared to controls; and the concentration of tumor-necrosis factor alpha ([TNF-α]) was positively correlated to the metabolic activity of the lung tumor as defined by the 2-deoxy-2-((18)F)fluoro-D-glucose ((18)FDG) positron emission tomography (PET) derived maximal standardized uptake values (SUV(max)). Finally, multivariate statistical modeling revealed that the concentration of N-acetyl-aspartate [NAA] in the occipital cortex was negatively associated with [TNF-α]. In conclusion, our data demonstrate that the cerebral metabolic status of patients with lung cancer is changed even prior to treatment. In addition, the association between inflammatory cytokines, SUV(max) and [NAA] points towards interactions between the cancer's inherent metabolic activity, systemic subclinical inflammation and brain function.

Propofol and thiopental do not interfere with regional cerebral blood flow response at sedative concentrations.

BACKGROUND: Anesthetics may affect the regional cerebral blood flow (rCBF) response associated with increased brain activity in humans. rCBF was measured as auditory stimulus rate was increased during propofol and thiopental administration. METHODS: After informed consent, 10 right-handed male volunteer participants (aged 33.5 +/- 10.4 yr, weighing 74.5 +/- 8.4 kg) received thiopental (n = 4) or propofol (n = 6) intravenously at stepwise target concentrations of propofol 1.2 and 2.5-3, or thiopental 4 and 7-9 microg/ml, representing sedative and hypnotic drug concentrations. The latter made volunteers unresponsive to voice or mild stimulation. Quantitative positron emission tomographic brain images were obtained at 0, 20, and 40 auditory words per minute at each drug concentration. Using SPM99 analysis, 10-mm spherical regions of interest were identified by peak covariation of word rate with rCBF across all conditions and drug concentrations. Individual mean rCBF responses in these and primary auditory cortex (Heschl's gyri) were obtained. RESULTS: Significant increases in rCBF with auditory word rate occurred in temporal lobes bilaterally at baseline (significance, T = 4.95). There was no change in this response during sedation (T = 5.60). During unresponsiveness seven of 10 participants had a diminished response in the left temporal lobe (T = 3.18). Global CBF, corrected for changes in PCO2 (3% .mmHg PCO2), was reduced 15% by sedation and 27% during unresponsiveness. CONCLUSION: The presence of propofol or thiopental does not affect the rCBF response to increasing stimulus rate during consciousness. Thus, changes in rCBF activation patterns with sedative concentrations of these drugs represent effects on brain activity itself. The neuroanatomical targets of drug effect on memory and attention may be revealed by changes in rCBF patterns associated with these cognitive activities.

Propofol-induced alpha rhythm.

The electroencephalographic effects of two intravenous sedative/hypnotic drugs, propofol and thiopental, were studied at three stable blood concentrations in 52 normal healthy volunteers. The higher concentration resulted in unresponsiveness (lack of response to auditory/tactile stimuli) in all subjects. This report describes the strong frontal-central rhythms apparent in this state using a quantitative description of oscillatory systems underlying the rhythm. These rhythms occur when sedative drug concentrations are greater than those producing the well-described increase in broadband beta-power associated with many sedative drugs. Propofol induces rhythms in the alpha-range, while thiopental produces rhythms in the beta-range. Quasistationary for a period of about 1 h, these rhythms exceed the baseline alpha-rhythm in power. By their resonant nature, these propofol-induced rhythms are analogous to 'the classic alpha-rhythm', but quantitative characteristics of the underlying oscillatory systems are different. Baseline properties of the oscillatory system underlying the initial resting alpha-rhythm recover completely as drug concentration decays to negligible values.

A neuroanatomical construct for the amnesic effects of propofol.

BACKGROUND: This study was designed to identify neuroanatomical locations of propofol's effects on episodic memory by producing minimal and maximal memory impairment during conscious sedation. Drug-related changes in regional cerebral blood flow (rCBF) were located in comparison with rCBF increases during a simple word memory task. METHODS: Regional cerebral blood flow changes were assessed in 11 healthy volunteers using H215O positron emission tomography (PET) and statistical parametric mapping (SPM99) at 600 and 1,000 ng/ml propofol target concentrations. Study groups were based on final recognition scores of auditory words memorized during PET scanning. rCBF changes during propofol administration were compared with those during the word memory task at baseline. RESULTS: Nonoverlapping memory effects were evident: low (n = 4; propofol concentration 523 +/- 138 ng/ml; 44 +/- 13% decrement from baseline memory) and high (n = 7; 829 +/- 246 ng/ml; 87 +/- 6% decrement from baseline) groups differed in rCBF reductions primarily in right-sided prefrontal and parietal regions, close to areas activated in the baseline memory task, particularly R dorsolateral prefrontal cortex (Brodmann area 46; x, y, z = 51, 38, 22). The medial temporal lobe region exhibited relative rCBF increases. CONCLUSIONS: As amnesia becomes maximal, rCBF reductions induced by propofol occur in brain regions identified with working memory processes. In contrast, medial temporal lobe structures were resistant to the global CBF decrease associated with propofol sedation. The authors postulate that the episodic memory effect of propofol is produced by interference with distributed cortical processes necessary for normal memory function rather than specific effects on medial temporal lobe structures.

Information loss over time defines the memory defect of propofol: a comparative response with thiopental and dexmedetomidine.

BACKGROUND: Sedative-hypnotic drugs impair memory, but details regarding the nature of this effect are unknown. The influences of propofol, thiopental, and dexmedetomidine on the performance of a task that isolates specific components of episodic memory function were measured. METHODS: Working (1 intervening item, 6 s) and long-term memory (10 intervening items, 33 s) were tested using auditory words in a continuous recognition task before and during drug administration. Eighty-three volunteer participants were randomly assigned to receive a constant target concentration of drug or placebo, producing sedative effects from imperceptible to unresponsiveness. Responsive participants were categorized as high or low performers, using a median split of long-term memory performance during drug administration. Recognition of words at the end of the study day was assessed. RESULTS: High performers had acquisition of material into long-term memory when drug was present at the same level as placebo. Retention of this material at 225 min was significantly less for propofol (39 +/- 23% loss of material) than for other drugs (17-23% loss; P < 0.01). Greater sedation in low performers was evident in multiple measures. Memory for words presented before drug was no different from that associated with placebo for all groups. CONCLUSIONS: Lack of retention of material acquired into long-term memory during propofol administration, associated with minimal sedation, seems to define drug-induced amnesia. Sedation seems to impair the acquisition or encoding of material into long-term memory. Therefore, the putative targets of drug-induced amnesia by propofol are processes associated with retention of material in long-term memory.