Effects of Rapid Increases of Desflurane and Sevoflurane to Concentrations of 1.5 MAC on Systemic Vascular Resistance and Catecholamine Response during Cardiopulmonary Bypass

Background: Airway irritation was hypothesized to trigger the transient cardiovascular stimulation associated with desflurane. The authors administered desflurane during cardiopulmonary bypass (CPB), thus avoiding airway contact, and compared the effects of rapid increases of desflurane to 1.5 MAC on systemic vascular resistance index (SVRI) and catecholamine response to those of 1.5 MAC sevoflurane.

Methods: Forty-eight patients, undergoing elective coronary bypass surgery, were randomly allocated to receive either desflurane or sevoflurane during hypothermic (32-33 [degree sign] Celsius) nonpulsatile CPB at exhaust gas concentrations of 1.5 MAC for 15 min. SVRI was calculated at baseline, 1, 2, 3, 4, 5, 7, 9, 12, and 15 min after starting volatile anesthetics' delivery. Plasma catecholamine concentrations were determined in 12 desflurane-treated patients and 12 sevoflurane-treated patients at baseline, 5, and 15 min.

Results: The time-course of Delta SVRI, (changes in SVRI from baseline), from baseline to 5 min was significantly different between desflurane- and sevoflurane-treated patients, whereas there was no difference from 7 to 15 min. In the desflurane group, SVRI from 1 to 7 min remained unchanged to baseline level, thereafter declining to significantly lower values at 9, 12, and 15 min compared with values from 0 to 5 min, whereas sevoflurane produced an immediate and significant reduction in SVRI. With desflurane, catecholamine concentrations remained unchanged to baseline level at 5 and 15 min; with sevoflurane, they decreased with time.     

Rapid Decline of Kidney Function Increases Cardiovascular Risk in the Elderly

Chronic kidney disease (CKD), defined at a specific time point, is an important risk factor for cardiovascular disease. Whether the rate of kidney function decline contributes additional cardiovascular risk is unknown. In the Cardiovascular Health Study, we compared the associations of changes in kidney function during the first 7 yr with the incidence of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD) during the subsequent 8 yr. We defined a rapid decline in cystatin C–based estimated GFR as >3 ml/min per 1.73 m²/yr, on the basis of determination at baseline, year 3, and year 7. Among eligible participants, 1083 (24%) had rapid kidney decline. The incidence of each type of cardiovascular event was significantly higher among patients with rapid decline (all P < 0.001). After multivariate adjustment for demographics, cardiovascular disease risk factors, and baseline kidney function, rapid kidney function decline was significantly associated with HF (adjusted hazard ratio [HR] 1.32; 95% confidence interval [CI] 1.13 to 1.53), MI (HR 1.48; 95% CI 1.21 to 1.83), and PAD (HR 1.67; 95% CI 1.02 to 2.75) but not with stroke (HR 1.19; 95% CI 0.97 to 1.45). The association of rapid decline with each outcome did not differ by the presence or absence of CKD. In conclusion, declining kidney function associates with higher risk for HF, MI, and PAD among patients with or without CKD.Chronic kidney disease (CKD) is an important risk factor for the development of heart failure (HF), myocardial infarction (MI), stroke, and peripheral arterial disease (PAD).^1–5 The use of cystatin C in older adults has extended these associations across a broader range of kidney function than could be appreciated with creatinine-based estimated GFR (eGFR). Nonetheless, the mechanisms underlying the association between CKD and cardiovascular risk remain incompletely determined. Current understanding of kidney–cardiovascular disease (CVD) relationships is limited by the measurement of kidney function on a single occasion. This approach fails to discriminate people with declining kidney function from those with diminished but stable kidney function. An association between dynamic changes in kidney function with cardiovascular events independent of both other cardiovascular risk factors and the current level of kidney function would add risk information and strengthen the argument that reduced kidney function has a causal role in CVD.In the Cardiovascular Health Study (CHS), a community-based cohort of ambulatory elderly individuals, kidney function was measured at the baseline visit and at years 3 and 7 of follow-up. In a recent article, we evaluated the associations of changes in kidney function using each measure with subsequent mortality risk.⁶ Using either cystatin C (eGFR_cys) or creatinine (eGFR_creat), annual eGFR declines of >3 ml/min per 1.73 m² were independently associated with elevated all-cause and cardiovascular mortality risk; however, no association was observed for milder changes in kidney function.In this study from CHS, we evaluated the associations of rapid decline in kidney function with the incidence of specific cardiovascular end points: HF, MI, stroke, and PAD. We hypothesized that rapid kidney function decline would have independent associations with higher incidence of each outcome but with the strongest association with HF on the basis of our previous studies using baseline kidney function.^7–9     

Renal Responses to Low-flow Desflurane, Sevoflurane, and Propofol in Patients

Background: The contributing factors that result in significant, postoperative proteinuria and glucosuria after low-flow isoflurane and sevoflurane anesthesia are unknown. The present study compared renal responses after anesthesia with desflurane (negligible metabolism), sevoflurane, or intravenous propofol.

Methods: Informed consent was obtained from 52 patients with American Society of Anesthesiologists physical status I-III (aged 36-81 yr). Patients with diabetes or renal insufficiency were excluded. Desflurane (n = 20) or sevoflurane (n = 22), without nitrous oxide, was given at 1 l/min fresh gas flow for elective surgical procedures lasting more than 2 h; 10 patients received propofol without nitrous oxide as the primary anesthetic. Blood and urine chemistries were obtained before surgery. Blood and 24-h urine collections were obtained for 3 days after surgery and were analyzed for liver and renal indices.

Results: Length of surgery averaged ~ 300 min (range, 136-750 min), minimum alveolar concentration-hour averaged 4.3 (range, 1.2-11.0), and infusion rates of propofol were 99-168 [mu]g [middle dot] kg-1 [middle dot] min-1. Plasma creatinine concentration did not change, plasma blood urea nitrogen decreased significantly, and significant increases in urine glucose, protein, and albumin occurred similarly in all groups. Mean (+/- SD) postoperative urine glucose values for day 1 after desflurane, sevoflurane, and propofol were 1.4 +/- 3.0, 1.1 +/- 2.1, and 1.9 +/- 2.6 g/d (normal, < 0.5 g/d). The average daily protein/creatinine ratios for postoperative days 2-3 after desflurane, sevoflurane, and propofol were 240 +/- 187, 272 +/- 234, and 344 +/- 243 (normal,< 150 mg/g). Regardless of anesthetic, there were significantly greater urine protein concentrations after surgical procedures in central versus peripheral regions.     

Forty-hertz Midlatency Auditory Evoked Potential Activity Predicts Wakeful Response during Desflurane and Propofol Anesthesia in Volunteers

Background: Suppression of response to command commonly indicates unconsciousness and generally occurs at anesthetic concentrations that suppress or eliminate memory formation. The authors sought midlatency auditory evoked potential indices that successfully differentiated wakeful responsiveness and unconsciousness.

Methods: The authors correlated midlatency auditory evoked potential indices with anesthetic concentrations permitting and suppressing response in 22 volunteers anesthetized twice (5 days apart), with desflurane or propofol. They applied stepwise increases of 0.5 vol% end-tidal desflurane or 0.5 [mu]g/ml target plasma concentration of propofol to achieve sedation levels just bracketing wakeful response. Midlatency auditory evoked potentials were recorded, and wakeful response was tested by asking volunteers to squeeze the investigator's hand. The authors measured latencies and amplitudes from raw waveforms and calculated indices from the frequency spectrum and the joint time-frequency spectrogram. They used prediction probability (PK) to rate midlatency auditory evoked potential indices and concentrations of end-tidal desflurane and arterial propofol for prediction of responsiveness. A PK value of 1.00 means perfect prediction and a PK of 0.50 means a correct prediction 50% of the time (e.g., by chance).

Results: The ~40-Hz power of the frequency spectrum predicted wakefulness better than all latency or amplitude indices, although not all differences were statistically significant. The PK values for ~40-Hz power were 0.96 during both desflurane and propofol anesthesia, whereas the PK values for the best-performing latency and amplitude index, latency of the Nb wave, were 0.86 and 0.88 during desflurane and propofol (P = 0.10 for ~40-Hz power compared with Nb latency), and for the next highest, latency of the Pb wave, were 0.82 and 0.84 (P < 0.05). The performance of the best combination of amplitude and latency variables was nearly equal to that of ~40-Hz power. The ~40-Hz power did not provide a significantly better prediction than anesthetic concentration; the PK values for concentrations of desflurane and propofol were 0.91 and 0.94. Changes of ~40-Hz power values of 20% (during desflurane) and 16% (during propofol) were associated with a change in probability of nonresponsiveness from 50% to 95%.     

Desflurane Reduces the Febrile Response to Administration of Interleukin-2

Background: Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response.

Methods: Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffe's F tests.

Results: Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 [degree sign]C [center dot] h on the control day to 2.1 +/- 2.3 [degree sign]C [center dot] h during 0.6 MAC and to -1.4 +/- 3.1 [degree sign]C [center dot] h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 [degree sign]C on the control day, 37.7 +/- 0.7 [degree sign]C during 0.6 MAC and 37.2 +/- 1.0 [degree sign]C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering.     

Ventilatory Response to Hypoxia in Humans: Influences of Subanesthetic Desflurane

Background: At low dose, the halogenated anesthetic agents halothane, isoflurane, and enflurane depress the ventilatory response to isocapnic hypoxia in humans. In the current study, the influence of subanesthetic desflurane (0.1 minimum alveolar concentration [MAC]) on the isocapnic hypoxic ventilatory response was assessed in healthy volunteers during normocapnia and hypercapnia.

Methods: A single hypoxic ventilatory response was obtained at each of 4 target end-tidal partial pressure of oxygen concentrations: 75, 53, 44, and 38 mmHg, before and during 0.1 MAC desflurane administration. Fourteen subjects were tested at a normal end-tidal partial pressure of carbon dioxide (43 mmHg), with 9 subjects tested at an end-tidal carbon dioxide concentration of 49 mmHg (hypercapnia). The hypoxic sensitivity (S) was computed as the slope of the linear regression of inspired minute ventilation (VI) on (100 - SP O2). Values are mean +/-SE.

Results: Sensitivity was unaffected by desflurane during normocapnia (control: S = 0.45+/-0.071 *symbol* min *symbol* sup -1 *symbol* % sup -1 vs. 0.1 MAC desflurane: S = 0.43+/-0.09 1 *symbol* min sup -1 *symbol* % sup -1). With hypercapnia S decreased by 30% during desflurane inhalation (control: S = 0.74+/-0.091 *symbol* min sup -1 *symbol* %1 vs. 0.1 MAC desflurane: S = 0.53+/-0.06 1 *symbol* min sup -1 *symbol* % sup -1; P < 0.05).     

Awakening Concentration of Desflurane Is Decreased in Patients with Obstructive Jaundice

Background: Some studies suggest that behavioral complications of cholestasis, such as fatigue and pruritus, may be associated with altered neurotransmission in the brain. Because inhaled anesthetics primarily act on ion channels and receptors on the neuronal cell membrane and alter synaptic transmission in the central nervous system, it is possible that altered sensitivity to inhaled anesthetics may occur in cholestatic patients. Therefore, the authors compared the minimum alveolar concentration (MAC)-awake of desflurane in obstructive jaundiced patients with the MACawake in nonjaundiced patients.

Methods: Patients underwent inhalational induction of anesthesia with desflurane. MACawake was determined in each patient by observing the response to a verbal command (open eyes on request). An end-tidal anesthetic concentration was maintained at an initial target level of 1.4% for 15 min before a command. If a positive response was observed, the concentration of desflurane was increased by 0.1% and again kept constant for 15 min. The verbal command was then continued. This process was repeated until an end-tidal concentration was reached at which the patient did not respond to command. The anesthetic concentration midway between the value permitting the response and that just preventing the response was defined as MACawake for each patient.

Results: The MACawake of desflurane for patients with obstructive jaundice (1.78 +/- 0.19%) was significantly less than those observed for the control group (2.17 +/- 0.25%; P < 0.001) and correlated significantly with serum total bilirubin (r = -0.67, P = 0.0004).     

芬太尼在异丙酚诱导期间对脑电双频指数及血压心率的影响

目的 :观察在异丙酚诱导期间 ,不同剂量芬太尼对脑电双频指数 (BIS)为参考指标的皮层功能状态的影响以及相应的血压心率变化。方法 :选择 40例ASAⅠ～Ⅱ级病人 ,随机分成四组 :Ⅰ组为对照组 ,Ⅱ、Ⅲ、Ⅳ组分别接受芬太尼 2 μg/kg、4μg/kg、8μg/kg ,静注生理盐水或芬太尼后 ,通过输液泵持续输注异丙酚使BIS稳定在 45± 5并维持 3分钟后插管。试验采用双盲法。结果 :置喉镜插管后 ,Ⅰ、Ⅱ组血压、心率较基础值明显升高 ,Ⅲ、Ⅳ组则升高不明显(P >0 0 5)、插管刺激使Ⅰ、Ⅱ、Ⅲ组BIS较插管前明显升高 ,而Ⅳ组BIS升高却不明显。SEF对插管刺激缺乏特异性变化。结论 :4μg/kg以上的芬太尼可以有效减弱插管所致的心血管反应 ,而 8μg/kg的芬太尼才可削弱置喉镜插管对皮层状态的激活 ,BIS不能预测气管插管引起的心血管反应     

预防气管拔管时的心血管反应（几种方法比较）

６０例静吸复合全麻病人，术毕具备拔管指征时，随机分为四组，即对照组，利多卡因组，安定利多卡因组和硝酸甘油组，分别于拔管前５ｍｉｎ、拔管发明主拔管后３ｍｉｎ、６ｍｉｎ测量ＳＢＰ、ＤＢＰ、ＭＡＰ、ＨＲ、ＲＰＰ。结果表明后，后两组能有效地预防拔管时的心血管反应。     

Propofol Increases Presynaptic Inhibition of Ia Afferents in the Intact Human Spinal Cord

Background: In vitro studies indicate that the primary molecular targets of propofol in the spinal cord are [gamma]-aminobutyric acid (GABA) type A receptors. Because of the complexity of the central nervous system, specific GABA-mediated effects have not yet been isolated in humans. Here, the authors used heteronymous Ia facilitation of the soleus H-reflex from the femoral nerve as a specific pathway involving GABA to demonstrate a presynaptic GABA-mediated effect of propofol in humans.

Methods: The study was performed in 10 volunteers aged 23-32 yr. The soleus H-reflex was evoked by stimulation of the tibial nerve in the popliteal fossa. The stimulation current was adjusted to yield an unconditioned H-reflex of 15% of the maximal muscle response to electric stimulation of the tibial nerve. The soleus H-reflex was conditioned by stimulating Ia afferents from the quadriceps femoris in the femoral triangle. The stimulus was applied 0.3-0.4 ms after the onset of facilitation, to assure a purely monosynaptic excitatory postsynaptic potential from quadriceps Ia afferents to the soleus motoneuron. At least 45 conditioned (femoral and tibial) and unconditioned (only tibial) stimuli were applied in random order. The authors compared the amount of heteronymous H-reflex facilitation under a concentration of 2 [mu]g/ml propofol with control values obtained before and after the propofol infusion.

Results: H-reflex facilitation due to the conditioning stimulus during propofol administration was significantly (P < 0.05, t test) decreased by an average of 43% in all patients in comparison with the control values.     

Cardiovascular Effects of Propofol in Dogs with Dilated Cardiomyopathy

Background: The authors tested the hypothesis that propofol improves left ventricular diastolic function in dogs with dilated cardiomyopathy by reducing left ventricular preload and afterload.

Methods: Seven dogs were instrumented for left ventricular and aortic pressures, aortic blood flow, and subendocardial segment length. Left ventricular afterload and contractility were quantified with aortic input impedance and preload recruitable stroke work, respectively. Diastolic function was evaluated with a time constant of left ventricular relaxation (tau); segment-lengthening velocities and time-velocity integrals during early left ventricular filling (dL/dtE and TVI-E, respectively) and atrial systole (dL/dtA and TVI-A, respectively); and a regional chamber stiffness constant (K). Dogs were paced at 240 beats/min for 18 +/- 3 days, and hemodynamics were recorded in sinus rhythm in the conscious state. Anesthesia was induced with propofol (5 mg/kg) and maintained with propofol infusions at 25, 50, and 100 mg [center dot] kg sup -1 [center dot] h sup -1, and hemodynamics were recorded after 15 min of equilibration at each dose.

Results: Propofol decreased mean arterial pressure, left ventricular end-diastolic pressure, and K but did not change heart rate. Propofol reduced total arterial resistance and increased total arterial compliance derived from aortic input impedance. Propofol also reduced preload recruitable stroke work. The lowest dose of propofol decreased tau. Propofol decreased dL/dtE and TVI-E and reduced the dL/dt-E/A and TVI-E/A ratios.     

Persistent Depression of Contractility and Vasodilation with Propofol but Not with Sevoflurane or Desflurane in Rabbits

Background: Propofol, sevoflurane, and desflurane may cause hemodynamic compromise during anesthesia and critical care management. The aim of the study was to compare these anesthetics during increased dose and recovery to maintenance level.

Methods: Anesthetized, open-chest New Zealand White rabbits were used to acquire dose-response curves with sevoflurane, desflurane, and propofol, followed by reduction to baseline infusion. Simultaneous high-fidelity left ventricular pressure and volume data were acquired during caval occlusion with a dual-field conductance catheter inserted via an apical stab. The preload recruitable stroke work and the end-diastolic pressure-volume relationship were used as the primary measures of contractility and diastolic function.

Results: The time-matched controls were stable over time. Propofol and desflurane but not sevoflurane caused dose-dependent reductions in myocardial contractility, although sevoflurane reduced contractility more at 1 minimal alveolar concentration. All anesthetics reduced mean arterial pressure, and significant recovery occurred for sevoflurane and desflurane but not for propofol. The end-diastolic pressure-volume relationship was increased by sevoflurane. Ejection fraction decreased with sevoflurane only. All anesthetics caused dose-dependent vasodilation, with recovery for desflurane and sevoflurane but not propofol. Heart rate was decreased with propofol without significant recovery. Propofol plasma concentrations remained elevated after dose return to baseline infusion rate, suggestive of distribution compartment saturation.     

小儿臂丛神经阻滞丙泊酚TCI的半数有效浓度

目的:测定小儿臂丛神经阻滞丙泊酚靶控输注的半数有效血浆靶控浓度。方法:择期臂丛麻醉下行前臂或手外科手术患儿,术前30min口服咪达唑仑镇静,序贯法靶控输注丙泊酚,初始血浆靶浓度设为5.0μg/mL,待患儿睫毛反射消失和对言语指令无反应时,行腋路臂丛神经阻滞。结果:丙泊酚TCI抑制小儿臂丛神经阻滞时患儿体动反应的半数有效血浆靶控浓度为3.9μg/mL,95%可信区间为3.6～4.2μg/mL。结论:口服咪达唑仑镇静下,丙泊酚抑制臂丛神经阻滞时患儿体动反应的半数有效血浆靶控浓度为3.9μg/mL。     

On-line Monitoring of End-tidal Propofol Concentration in Anesthetized Patients

Background: Propofol (2,6-diisopropylphenol) has some volatility, so it can be detected in expired breath of individuals receiving intravenous propofol. This study measured volatile propofol exhaled by patients and investigated the relation between exhaled and plasma propofol concentrations.

Methods: Nineteen patients with American Society of Anesthesiologists physical status I or II who were undergoing elective surgery participated in this two-part study. In study 1 (n = 11), anesthesia was induced with 2 mg/kg propofol, 0.1 mg/kg vecuronium, and 2 [mu]g/kg fentanyl. After intubation, propofol was administered continuously for 60 min at each of three rates: 3, 6, and 9 mg [middle dot] kg-1 [middle dot] h-1. Blood samples were obtained just before each change in the infusion rate, and the plasma concentrations of propofol were measured. The exhaled propofol concentration was measured continuously by means of proton transfer mass spectrometry. End-tidal propofol concentrations during blood sampling were averaged and compared with plasma propofol concentrations. In study 2 (n = 8), after induction of anesthesia, patients received a bolus injection of 2 mg/kg propofol, and the exhaled propofol concentration was measured.

Results: Volatile propofol was detected in expired gas from all study patients. From study 1, the authors obtained 24 paired data points, i.e., concentrations of end-tidal and plasma propofol. With Bland-Altman analysis, bias +/- precision was 5.2 +/- 10.4 with 95% limits of agreement of -15.1 and 25.6. In study 2, the exhaled propofol concentration curve showed an obvious peak in all patients.