Pressure pain thresholds in volunteers and herniorrhaphy patients

Pressure algometry is a method to estimate pressure pain sensitivity in tissues. The aim of the present study was to evaluate the reproducibility of pressure pain thresholds (PPT) in the abdominal integument and to evaluate the use of pressure algometry as a measure of wound tenderness following surgery. PPT was determined in 20 healthy volunteers on two separate examinations, and in 14 patients at the incisional site before and following inguinal herniotomy. In volunteers, PPT was higher for men than for women, and no difference was observed between the first and second day of examination. In surgical patients a significant decrease in PPT was observed following operation. Morphine 0.07 mg/kg caused a slight but significant increase in PPT. Pressure algometry may be useful to study nociceptive mechanisms and the dynamics of wound pain in surgical patients.     

The effects of dexmedetomidine on neuromuscular blockade in human volunteers

The neuromuscular effects of dexmedetomidine in humans are unknown. We evaluated the effect of dexmedetomidine on neuromuscular block and hemodynamics during propofol/alfentanil anesthesia. During propofol/alfentanil anesthesia, the rocuronium infusion rate was adjusted in 10 volunteers to maintain a stable first response (T1) in the train-of-four sequence at 50% +/- 3% of the pre-rocuronium value. Dexmedetomidine was then administered by computer-controlled infusion, targeting a plasma dexmedetomidine concentration of 0.6 ng/mL for 45 min. The evoked mechanical responses of the adductor pollicis responses (T1 response and T4/T1 ratio), systolic blood pressure (SBP), heart rate (HR), and transmitted light through a fingertip were measured during the dexmedetomidine infusion and compared with predexmedetomidine values using repeated-measures analysis of variance and Dunnett's test. Plasma dexmedetomidine levels ranged from 0.68 to 1.24 ng/mL. T1 values decreased during the infusion, from 51% +/- 2% to 44% +/- 9% (P < 0.0001). T4/T1 values did not change during the infusion. Plasma rocuronium concentrations increased during the infusion (P = 0.02). Dexmedetomidine increased SBP (P < 0.001) and decreased HR (P < 0.001) (5-min median values) during the infusion compared with values before the infusion. Dexmedetomidine increased the transmitted light through the fingertip by up to 41% +/- 8% during the dexmedetomidine infusion (P < 0.001).We demonstrated that dexmedetomidine (0.98 +/- 0.01 microg/kg) increased the plasma rocuronium concentration, decreased T1, increased SBP, and decreased finger blood flow during propofol/alfentanil anesthesia. We conclude that dexmedetomidine-induced vasoconstriction may alter the pharmacokinetics of rocuronium. IMPLICATIONS: We studied the effect of an alpha2-agonist (dexmedetomidine) on rocuronium-induced neuromuscular block during propofol/alfentanil anesthesia. We found that the rocuronium concentration increased and the T1 response decreased during the dexmedetomidine administration. Although these effects were statistically significant, it is unlikely that they are of clinical significance.     

The effects of remifentanil on cerebral capacity in awake volunteers

Remifentanil, a short-acting potent mu-opioid agonist proposed for intraoperative analgesia but also for postoperative pain therapy, has not been investigated with regard to the effects of the drug on cerebral capacity in awake humans. We assessed cerebral capacity noninvasively by means of phase-contrast magnetic resonance imaging measurement of systolic cerebrospinal fluid peak velocity in the aqueduct of Sylvius before and during infusion of remifentanil (0.1 microg. kg(-1). min(-1) IV) in normocapnic humans. Remifentanil had no significant effect on systolic cerebrospinal fluid peak velocity as compared with baseline (mean +/- SD): baseline, -4.3 +/- 1.3 cm/s versus remifentanil (0.1 microg. kg(-1). min(-1)): -4.7 +/- 1.0 cm/s. Small-dose remifentanil (0.1 microg. kg(-1). min(-1)) did not influence cerebral capacity in healthy, awake volunteers free of intracranial pathology. IMPLICATIONS: Knowledge about the influence of remifentanil on cerebral capacity is crucial before routine use of the drug in neuroanesthesia. Thus, we assessed the influence of remifentanil on cerebral capacity noninvasively by means of phase-contrast magnetic resonance imaging measurement of systolic cerebrospinal fluid peak velocity in the aqueduct of Sylvius in humans.     

Vascular effects of urapidil administrated during extracorporeal circulation]

Urapidil exerts a combined central sympathetic and peripheral alpha-1 adrenergic receptor inhibition. Urapidil induces arterial vasodilation but its effects on venous capacitance are more difficult to assess. During cardiopulmonary bypass with constant perfusion index (2.4 l.min-1 x m-2) total peripheral resistance varies similarly as to arterial pressure and, as the apparatus venous reservoir is filled continuously by simple gravity from the right atrium, a decrease in venous blood reservoir level reflects an increased venous capacitance. Twenty-six patients undergoing cardiac surgery were anaesthetized with fentanyl and midazolam and randomly assigned to one of two groups. During normothermic cardiopulmonary bypass, group 1 was administered i.v. urapidil 12.5 mg and group 2 a placebo. In group 1, arterial pressure decreased by 33 +/- 14% (mean +/- SD) at the second minute while total peripheral resistance decreased from 1,384 +/- 255 to 927 +/- 193 dyn.s.cm-5. Then this two parameters regained group 2 values after the eighth minute. Reservoir blood level was lower in group 1 than in group 2 from the second to the eight minute (p < 0.05) with maximum effect at 7 minutes. It is concluded that urapidil exerts arterial and venous dilation. Its arterial effects seem greater during normothermic cardiopulmonary bypass than in normal conditions and its maximum venous effects seem to occur after its maximum arterial effects. The short duration of action may be due to the small dose administered.     

The effects of subanaesthetic concentrations of xenon in volunteers

This study reports the subjective, psychomotor and physiological properties of subanaesthetic concentrations of xenon. Ten healthy male volunteers received either xenon or nitrous oxide in a randomised crossover study design. The subjects breathed either xenon (Xe) or nitrous oxide (N2O) from a closed circuit breathing system, according to a randomised, double-blind protocol. The concentration of xenon required to produce sedation, ranged between 27 and 45% (median 35%). All subjects completed the xenon protocol. Subjects were tested using the Critical Flicker Fusion test and derived electroencephalogram parameters, however, neither test was found to reliably predict sedation. The respiratory rate decreased markedly during sedation with xenon. The subjects did not experience any airway irritability (coughing, breath-holding or laryngospasm) during administration of either gas. One subject required anti-emetic treatment in the N2O group compared to none in the Xe group. Eight subjects reported that they found sedation with xenon pleasant and preferable to nitrous oxide. Xenon sedation was well tolerated and was not associated with any adverse physiological effects, however, it was reported to be subjectively dissimilar to nitrous oxide.     

The metabolic effects of oral tizanidine in healthy volunteers

This pilot study compared the metabolic effects of placebo and 6 mg and 12 mg of oral tizanidine in random double-blind cross-over fashion in five healthy volunteers.
The metabolic measurements were made with a portable metabolic chart (Deltatrac, Datex/Instrumentarium, Helsinki, Finland). Heart rate (HR), systolic (BPS), mean (BPM) and diastolic (BPD) blood pressure were measured noninvasively. Subjective assessment of tiredness and dryness of mouth were measured by using visual analogue scales (VAS).
There were no statistically significant differences in tiredness or dryness of mouth between the groups. BPD decreased significantly after both doses of tizanidine when compared to placebo (by an average of 12% after 6 mg of tizanidine and 15% after 12 mg of tizanidine from the baseline). Oxygen consumption and energy expenditure decreased significantly after 6 and 12 mg of tizanidine when compared to placebo. The average decrease in oxygen consumption was 3% after 6 mg of tizanidine and 8% after 12 mg of tizanidine, when compared to the baseline. Energy expenditure decreased by an average of 5% after 6 mg of tizanidine and 9% after 12 mg of tizanidine, when compared to the baseline. There were no other statistically significant differences between the groups.
This study indicates that 6 and 12 mg of oral tizanidine can be useful for reducing energy expenditure and oxygen comsumption without prominent cardiovascular effects.     

The effects of glycopyrrolate on oral mucous host defenses in healthy volunteers

We studied the effects of glycopyrrolate on oral mucous host defenses. Single IV doses of glycopyrrolate (4 microg/kg) or placebo were administered to 12 healthy volunteers in a randomized, double-blinded, cross-over study. Salivary flow rates and the concentrations/activities of total protein, amylase, and nonimmunologic (lysozyme, lactoferrin, myeloperoxidase, total salivary peroxidase, and thiocyanate) and immunologic (total immunoglobulin A, immunoglobulin G, and immunoglobulin M) mucous host defense factors were determined for paraffin-stimulated whole saliva before and 1, 3, 6, 12, 24, and 48 h after drug administration. Glycopyrrolate serum concentrations were determined before and 2, 4, 6, 10, 15, and 30 min and 1, 2, 3, 6, 12, and 24 h after IV drug injection. Salivary flow rates were decreased significantly for 12 h after glycopyrrolate injection, compared with saline injection. The concentrations of immunologic and nonimmunologic defense factors were increased in the glycopyrrolate group, and differences between the groups were found for all factors (P < 0.05-0.001) except lysozyme and total salivary peroxidase. In contrast, because of the reduced flow rate, the output of all defense factors into the saliva was decreased after glycopyrrolate injection, compared with saline injection. Glycopyrrolate thus decreases the output of salivary host defense factors into the oral cavity. Implications: Glycopyrrolate induces long-lasting hyposalivation and decreases the secretion of salivary immunologic and nonimmunologic defense factors in healthy volunteers.     

Hypnosis increases heat detection and heat pain thresholds in healthy volunteers.

BACKGROUND AND OBJECTIVES: Hypnosis has been reported to induce analgesia and to facilitate anesthesia. To date, hypnotic-induced analgesia has had little explanation and it has even been questioned. The current study was thus designed to investigate the effect of hypnotic suggestion on thermal-detection thresholds, heat pain, and heat-pain tolerance thresholds. METHODS: In 15 healthy volunteers, enrolled in a randomized cross-over study, thermal thresholds were investigated in 2 sequences of measurements, under waking and hypnotic states, using a thermal stimulator. RESULTS: Heat detection and heat-pain thresholds were increased under hypnosis (from 34.3 +/-.9 degrees C to 36.0 +/- 2.9 degrees C and 45.0 +/- 3.7 degrees C to 46.7 +/- 2.7 degrees C, respectively, P <.05), whereas heat-pain tolerance and cold-detection thresholds were not statistically changed. CONCLUSION: These results indicate that hypnosis may partly impair the detection of A delta and C fibers stimulation, potentially explaining its analgesic effect.     

尼卡地平或乌拉地尔在冠状动脉旁路移植术转流中控制血压效果的研究

目的　比较尼卡地平或乌拉地尔在体外循环中控制血压的效果及其对血液动力学的影响。方法　 60例冠状动脉旁路移植术 ( CABG)病人在体外循环 ( CPB)中平均动脉压 ( MAP)升至80 mm Hg( 1k Pa=7.5 mm Hg)时接受尼卡地平或乌拉地尔治疗。60例病人随机分为尼卡地平组或乌拉地尔组 ,每组 3 0例 ;另设同时期同类病人 3 0例作为对照组。观察两药起效时间 ,维持 MAP在 ( 70±5 ) mm Hg所需剂量 ,降压期间对人工肺血面的影响 ,停机后的血液动力学及混合静脉血氧饱和度( SvO2 )变化。结果　将 MAP从 80 m m Hg降至 70 m m Hg,应用尼卡地平 4μg· kg- 1 · min- 1 所需时间为 ( 2 .4± 1.1)分 ,维持 MAP在 ( 70± 5 ) m m Hg所需剂量为 ( 1.1± 0 .5 ) μg·kg- 1· m in- 1。应用乌拉地尔 90 μg· kg- 1· min- 1所需时间为 ( 2 .8± 1.0 )分 ,维持 MAP在 ( 70± 5 ) mm Hg所需剂量为 ( 5 0 .8±14 .4 ) μg· kg- 1· min- 1 ,但有 2例耐药 ,需不断增加剂量方能控制血压。尼卡地平组 19例 ( 63 % ) ,乌拉地尔组 2 2例 ( 73 % )心脏自动复跳 ,两组的自动复跳率均高于对照组 ( 4 6.2 % ) ( P<0 .0 5 ) ,但两组之间无差异 ( P>0 .0 5 )。停机后两组外周阻力 ( SVR)较 CPB前均明显下降 ( P<0 .0 1) ,每搏量 ( SV)     

The effects of carbon dioxide on pulmonary mechanics in hyperventilating, normal volunteers.

Transpulmonary pressure, air flow, and end-tidal carbon dioxide levels were measured in normal human volunteers during hypocapnic, eucapnic, and hypercapnic hyperventilation. Respiratory rate and tidal volumes were well matched at a minute ventilation of 52 L. on three inspired gas mixtures: 21 per cent oxygen and 79 per cent nitrogen; 5 per cent carbon dioxide, 21 per cent oxygen and 74 per cent nitrogen; and 12 per cent carbon dioxide, 21 per cent oxygen and 67 per cent nitrogen. Respiratory rate, tidal volume, lung compliance, resistance, and resistive work per liter were calculated with a digital computer. In 13 experiments in 7 normal volunteers, no net bronchoconstriction or bronchodilatation was observed when eucapnic hyperventilation was compared to hypocapnic or hypercapnic hyperventilation. During hyperventilation of this degree, a change in bronchomotor tone owing to alteration in arterial or alveolar PCO2 either does not occur or else is masked by other reflexes or mechanical factors acting on the bronchi.     

The effects of angiotensin-converting enzyme inhibition on the urinary excretion of NTproBNP in male volunteers

AIMS: This study was designed to test if the renal excretion of the N-terminal prohormone of the B-type natriuretic peptide (NTproBNP) is modulated by angiotensin-converting enzyme inhibition (ACE-I). METHODS: Following 7 days on a sodium-enriched diet and an induction period of 4 days with incremental dosages of enalapril (2.5, 5, 7.5, 10 mg) or placebo, 10 healthy subjects underwent crossover and double-blind treatment with 20 mg enalapril sodium or placebo at 8:00 h. After 4 h (at 12:00 h), 20 ml.kg(-1) NaCl 0.9% was infused over 60 min. Hemodynamics were determined and blood and urine were sampled at 8:00, 12:00, 13:00, 14:00, 16:00, and 18:00 h. Angiotensin II (AII), NTproANP, and NTproBNP were determined by radio- and electrochemiluminescence immunoassays. RESULTS: In the whole group, ACE-I led to a lower arterial blood pressure during the fourth day of induction and during the time from 8:00 to 16:00 h, a decrease in AII levels from 8:00 to 14:00 h (p < 0.05), and to a higher cumulative urine output (p < 0.05) in comparison with control. Neither cumulative sodium nor urinary NTproBNP/creatinine excretion were significantly increased after ACE-I. However, a subgroup of 6 volunteers - showing an increase in sodium excretion after ACE-I - also demonstrated lower AII levels at 13:00 h, a higher cumulative urine flow, and a higher urinary NTproBNP/creatinine excretion in comparison with control (all: p < 0.05). CONCLUSIONS: This suggests that the renal excretion of NTproBNP is modified by enalapril. However, it remains to be determined if this is a direct effect of ACE-I, the decrease in arterial blood pressure, or other potentially confounding variables like bradykinin or endopeptidase activity.     

The effects of nitrous oxide and oxygen on transient hyperemic response in human volunteers.

The aim of this study was to determine the effects of breathing 100% oxygen or 50% nitrous oxide in oxygen on the indices of cerebral autoregulation derived from the transient hyperemic response (THR) test in human volunteers. Data were analyzed from nine healthy subjects. Middle cerebral artery (MCA) blood flow velocity (FV) was measured by transcranial Doppler ultrasound, and the THR test was performed using 10-s compression of the common carotid artery. Continuous measurement of P(ETCO2) and expired fractions of oxygen (F(ETO2)) and nitrous oxide (F(ETN2O)) was established, and mean arterial pressure (MAP) was recorded at 2-min intervals. All measurements were performed while the volunteers were breathing room air and were repeated 10 min after achieving F(ETO2) >0.95 and 10 min after achieving F(ETN2O) 0.48-0.52. Two indices derived from the THR test, the transient hyperemic response ratio (THRR) and strength of autoregulation (SA), were used to assess cerebral autoregulation. P(ETCO2) and mean arterial pressure did not change significantly throughout the study period. Breathing 100% oxygen did not change MCA FV, THRR, or SA. Inhalation of nitrous oxide resulted in a marked and significant increase in the MCA FV (from 48+/-9 to 72+/-8 cm/s; mean +/- SD) and a significant decrease in the THRR (from 1.5+/-0.2 to 1.2+/-0.1) and the SA (from 1.0+/-0.1 to 0.8+/-0.1) (P<0.05 for all). We conclude that breathing 50% nitrous oxide in oxygen results in both a significant increase in MCA FV and impairment of transient hyperemic response. IMPLICATIONS: Our study suggests that nitrous oxide impairs cerebral autoregulation and may have implications for its use in neurosurgical anesthesia and for interpretation of the results from studies of anesthetics in which nitrous oxide is used in the background.     

The effects of malignant glioma on the EEG and seizure thresholds: An experimental study

Summary Generalised or partial seizures are a common problem with many supratentorial gliomas. Their underlying pathophysiological mechanisms are poorly understood. To investigate this problem clinical and EEG seizure thresholds were investigated in experimental rodent gliomas using the epileptogenic drug pentylenetetrazole (PTZ). Mixed C6/A15A5 malignant gliomas were grown in adult Wistar rats after unilateral stereotactic implantation of a 50 50 cell mix into the caudoputaminal region. Eleven to 14 days later EEG (raw and spectrally analysed) was recorded bilaterally from the frontal and parietal regions under mixed -chloralose and urethane anaesthesia. Baseline EEG (15 minutes), EEG during and after (30 minutes) PTZ infusion (100 l/min) and the time to appearance of seizure manifestations after starting PTZ were recorded. Fourteen animals were studied (5 normal, 5 with tumours, 4 sham implants) and mean BP, PaCO₂, PaO₂ and temperature were similar in the three groups. Baseline raw EEG showed predominate slow wave activity with lower amplitude and less spontaneous activity overlying tumours. Following PTZ infusion a sequence of vibrissal twitching (following a mean of 14.5 mg/kg PTZ in control and sham animals); jaw/nasal twitches (17.5 mg/kg); fore and hind limb jerking (46 mg/kg); myoclonic jerking (47 mg/kg); and status (77.5 mg/kg) was observed. The seizure thresholds for all PTZ induced seizure phenomena were, except for status epilepticus, highest in the tumour bearing animals. The time to 70% seizure activity on the EEG was also significantly longer in the tumour bearing animals. Spectral analysis of the EEG, although showing increased alpha and theta activity after PTZ infusion, did not discriminate between the three experimental groups either before or after PTZ activation. These studies have confirmed that experimental gliomas alter baseline EEG and both the EEG and behavioural response to PTZ. The reasons for the raised seizure threshold in the glioma bearing animals and the relevance of this experimental paradigm to human tumour associated epilepsy are discussed.     

The thermoregulatory threshold in humans during halothane anesthesia

Although suppression of thermoregulatory mechanisms by anesthetics is generally assumed, the extent to which thermoregulation is active during general anesthesia is not known. The only thermoregulatory responses available to anesthetized, hypothermic patients are vasoconstriction and non-shivering thermogenesis. To test anesthetic effects on thermoregulation, the authors measured skin-surface temperature gradients (forearm temperature--finger-tip temperature) as an index of cutaneous vasoconstriction in unpremedicated patients anesthetized with 1% halothane and paralyzed with vecuronium during elective, donor nephrectomy. Patients were randomly assigned to undergo maximal warming (warm room, humidified respiratory gases, and warm intravenous fluids; n = 5) or standard temperature management (no special warming measures; n = 5). Skin-surface temperature gradients greater than or equal to 4 degrees C were prospectively defined as significant vasoconstriction. Normothermic patients [average minimum esophageal temperature = 36.4 +/- 0.3 degrees C (SD)] did not demonstrate significant vasoconstriction. However, each hypothermic patient displayed significant vasoconstriction at esophageal temperatures ranging from 34.0 to 34.8 degrees C (average temperature = 34.4 +/- 0.2 degrees C). These data indicate that active thermoregulation occurs during halothane anesthesia, but that it does not occur until core temperature is approximately equal to 2.5 degrees C lower than normal. In two additional hypothermic patients, increased skin-temperature gradients correlated with decreased perfusion as measured by a laser Doppler technique. Measuring skin-surface temperature gradients is a simple, non-invasive, and quantitative method of determining the thermoregulatory threshold during anesthesia.     

Acute effects of urapidil on left ventricular function in hypertensive patients: comparison with clonidine using radionuclide angiography

We have studied the effects of urapidil 0.4 mg kg^–1 i.v.and clonidine 2.5 µg ^–1 i.v. on left ventricularvolume and function in 20 patients with chronic coronary arterydisease and essential hypertension. Patients were studied using^99mtechnetium radio-nuclide angiography with first-pass andECG-gated equilibrium blood-pool techniques and non-invasivesphygmomanometry. Administration of both urapidil and clonidinecaused a similar decrease in mean arterial pressure (20%), associatedwith an equivalent reduction in systemic vascular resistance.Despite the decrease in mean arterial pressure, heart rate didnot change after administration of clonidine, but there wasan early and transient increase of 13% after urapidil. Therewere no changes in cardiac index, but in contrast with clonidine,urapidil caused a decrease in stroke index. In both groups,global left ventricular ejection fraction did not change. Urapidilproduced a mean decrease in end-diastolic volume of 8% and amean decrease in end-systolic volume of 13%, in contrast withclonidine which caused little change. Reduced arterial pressure,systemic vascular resistance and preload after urapidil 0.4mg kg^–1 i.v., associated with lack of prolonged tachycardiaand preserved global left ventricular performance, may haveobvious clinical implications in anaesthesia.