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Biomedical subjects

Andrea Paris

Publications and source records attributed to Andrea Paris.

10 recordsLinked to original sources

Monitoring consciousness in intensive care medicine.

Sedation and analgesia are important components of care for critically ill patients. Avoiding over-as well as undersedation is of utmost importance as both states carry considerable risks and may influence outcome. The management of sedation has changed dramatically over the past two decades from providing a dosage level by which the patient was kept in a deep stage of anaesthesia to a current dosing strategy allowing the administration of drugs in line with individual need, resulting in most cases in a slightly sedated, cooperative patient. The importance of monitoring the level of sedation and analgesia has only recently been realised. Most importantly, regularly determining the appropriate level of sedation and analgesia as well as monitoring the desired level of sedation will help to minimise the adverse effects of sedation. Clinical sedation scales are, however, subjective, and most lack proper validation. Thus, an objective measure of sedation, such as the use of processed electroencephalogram (EEG) parameters is desirable. Processed EEG algorithms such as the bispectral index were initially introduced into clinical practice as a tool to assess the depth of anaesthesia objectively in the operating room. However, patients under general anaesthesia differ from those in an intensive care unit. Accordingly, most results from studies evaluating the performance of processed EEG parameters in critically ill patients have not been satisfactory. At present, monitoring sedation with processed EEG parameters cannot generally be recommended. However, in special situations such as deep sedation and neuromuscular blockade, in which clinical sedation scales are prone to failure, the bispectral index may help to assess the level of sedation.

Analgesia↗

The effects of dexmedetomidine on perinatal excitotoxic brain injury are mediated by the alpha2A-adrenoceptor subtype.

We performed the current study in mice lacking individual alpha2-adrenoceptor subtypes to elucidate the contribution of alpha(2)-adrenoceptor subtypes to the neuroprotective properties of dexmedetomidine in a model of perinatal excitotoxic brain injury. On postnatal Day 5, wild-type mice and mice lacking alpha2A-adrenoceptor (alpha2A-KO) or alpha2C-adrenoceptor subtypes (alpha2C-KO) were randomly assigned to receive dexmedetomidine (3 microg/kg) or phosphate-buffered saline intraperitoneally. Thirty minutes after the intraperitoneal injection, the glutamatergic agonist ibotenate (10 microg) was intracerebrally injected, producing transcortical necrosis and white matter lesions that mimic perinatal human hypoxic-like lesions. Quantification of the lesions was performed on postnatal Day 10 by histopathologic examination. Dexmedetomidine reduced mean lesion size in the cortex of wild-type mice and alpha2C-KO mice by 44% and 49%, respectively. Ibotenate-induced white matter lesions were reduced by 71% (wild-type mice) and 75% (alpha2C-KO mice) after pretreatment with dexmedetomidine. In contrast, in alpha2A-KO mice, dexmedetomidine did not protect against the cortical excitotoxic insult, and white matter lesions were even more pronounced (82% increase of mean lesion size). Dexmedetomidine provides potent neuroprotection in a model of perinatal excitotoxic brain damage. This effect was completely abolished in alpha2A-KO mice, suggesting that the neuroprotective effect is mediated via the alpha2A-adrenoceptor subtype.

Adrenergic alpha-Agonists↗

Dexmedetomidine in anaesthesia.

PURPOSE OF REVIEW: The development of dexmedetomidine, a potent and highly selective alpha2-adrenoceptor agonist, has created new interest in the use of alpha2-adrenoceptor agonists, and has led to its evaluation in various yet non-approved perioperative settings. The current review focuses on the usefulness of dexmedetomidine in anaesthesia practice. RECENT FINDINGS: Recently acquired knowledge and experience with dexmedetomidine in perioperative use will be presented and discussed in the context of known pharmacological properties. SUMMARY: Dexmedetomidine offers beneficial pharmacological properties, providing dose-dependent sedation, analgesia, sympatholysis and anxiolysis without relevant respiratory depression. The side-effects are predictable from the pharmacological profile of (2-adrenoceptor agonists. In particular, the unique sedative properties of dexmedetomidine resulted in several interesting applications in anaesthesia practice, promising benefits in the perioperative use of this compound. However, dexmedetomidine was approved for sedation in the intensive care unit in the USA in 1999, and administration in anaesthesia practice remains an 'off-label' use. Further studies are needed to establish the role of dexmedetomidine in the perioperative period.

Journal Article↗

Comparison of two bispectral index algorithms in monitoring sedation in postoperative intensive care patients.

OBJECTIVE: Comparison of two versions of bispectral index (BIS) derived from the electroencephalogram in mechanically ventilated and continuously sedated patients after major abdominal surgery. DESIGN: Prospective, cohort, observational, unblinded study. SETTING: Surgical intensive care unit of a university hospital. PATIENTS: Forty-six patients undergoing major abdominal surgery scheduled for postoperative mechanical ventilation and continuous sedation. INTERVENTIONS: Patients were continuously sedated using propofol and sufentanil. MEASUREMENTS AND MAIN RESULTS: Electrodes for determination of BIS were placed at the forehead of the patients according to the manufacturer's specifications immediately after arrival to the intensive care unit. The level of consciousness was assessed every 2 hrs by a clinical sedation scale (Ramsay sedation scale, levels 1-6). BIS, electromyographic activity, and signal quality index were recorded simultaneously at the same time as the Ramsay scale for 24 hrs or until patients were ready for extubation. BIS (version 2.10) and BIS XP (version 3.12) were determined at 2-hr intervals. BIS and BIS XP showed a high correlation of readings (rs = .79, p < .01). However, the methods did not yield identical results. Both variables were significantly influenced by electromyographic activity, especially at high values, whereas there was only a weak correlation with body temperature. Some of the deeply sedated patients (Ramsay 5 or 6) had BIS readings >80 (BIS, 16%; BIS XP, 13%; p = not significant). CONCLUSIONS: The newer algorithm BIS XP did not perform better than the previous version BIS in patients after major surgery who were mechanically ventilated and sedated on an intensive care unit. This precludes the use of BIS or BIS XP for distinguishing, among deeply sedated ICU patients, those with and without preserved cerebral electrical activity.

Algorithms↗

The effect of meperidine on thermoregulation in mice: involvement of alpha2-adrenoceptors.

Meperidine has potent antishivering properties. The underlying mechanisms are not fully elucidated, but recent investigations suggest that alpha2-adrenoceptors are likely to be involved. We performed the current study to investigate the effects of meperidine on nonshivering thermogenesis in a model of thermoregulation in mice. After injection (0.1 mL/kg intraperitoneally) of saline, meperidine (20 mg/kg), the specific alpha2-adrenoceptor antagonist atipamezole (2 mg/kg), plus saline or atipamezole plus meperidine, respectively, mice were positioned in a Plexiglas chamber. Rectal temperature and mixed expired carbon dioxide were measured after provoking thermoregulatory effects by whole body cooling. Maximum response intensity of nonshivering thermogenesis and the thermoregulatory threshold for nonshivering thermogenesis, which was defined as the temperature at which a sustained increase in expiratory carbon dioxide can be measured, were investigated. Meperidine significantly decreased the threshold of nonshivering thermogenesis (36.6 degrees C +/- 0.7 degrees C) versus saline (37.9 degrees C +/- 0.6 degrees C) and versus atipamezole plus saline (37.8 degrees C +/- 0.4 degrees C; P <0.01). This effect was abolished after administration of meperidine combined with atipamezole (37.7 degrees C +/- 0.6 degrees C; P <0.05). Meperidine did not decrease the maximum intensity of nonshivering thermogenesis. The results suggest a major role of alpha2-adrenoceptors in the inhibition of thermoregulation by meperidine in mice.

Adrenergic alpha-Antagonists↗

Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery.

Volatile anesthetics exert cardioprotective properties in experimental and clinical studies. We designed this study to investigate the effects of sevoflurane on left ventricular (LV) performance during minimally invasive direct coronary artery bypass grafting (MIDCAB) without cardiopulmonary bypass. Fifty-two patients scheduled for MIDCAB surgery were randomly assigned to a propofol or a sevoflurane group. Apart from the anesthetics used, there was no difference in surgical and anesthetic management. After determination of cardiac troponin T, creatine kinase, and creatine kinase MB, electrocardiographic (ECG) data and echocardiography variables (myocardial performance index and early to atrial filling velocity ratio) the left anterior descending coronary artery (LAD) was clamped until anastomosis with the left internal mammary artery was completed. During LAD occlusion and during reperfusion, echocardiography measurements were repeated. Blood samples were obtained repeatedly for up to 72 h. After LAD occlusion, myocardial performance index and early to atrial filling velocity ratio in the propofol group deteriorated significantly from 0.40 +/- 0.12 and 1.29 +/- 0.35 to 0.49 +/- 0.10 and 1.13 +/- 0.22, respectively, whereas there was no change in the sevoflurane group. In the propofol group myocardial performance index remained increased (0.47 +/- 0.11) compared with baseline during reperfusion. There were no significant differences in ECG and laboratory values between groups. In conclusion, during a brief period of ischemia in patients undergoing MIDCAB surgery, sevoflurane preserved myocardial function better than propofol.

Adult↗

Neuroendocrine stress response and heart rate variability: a comparison of total intravenous versus balanced anesthesia.

Attenuating intraoperative stress is a key factor in improving outcome. We compared neuroendocrine changes and heart rate variability (HRV) during balanced anesthesia (BAL) versus total IV anesthesia (TIVA). Forty-three patients randomly received either BAL (sevoflurane/remifentanil) or TIVA (propofol/remifentanil). Depth of anesthesia was monitored by bispectral index. Stress hormones were measured at 7 time points (P1 = baseline; P2 = tracheal intubation; P3 = skin incision; P4 = maximum operative trauma; P5 = end of surgery; P6 = tracheal extubation; P7 = 15 min after tracheal extubation). HRV was analyzed by power spectrum analysis: very low frequency (VLF), low frequency (LF), high frequency (HF), LF/HF ratio, and total power (TP). LF/HF was higher in TIVA at P6 and TP was higher in TIVA at P3-7 (P3: 412.6 versus 94.2; P4: 266.7 versus 114.6; P5: 290.3 versus 111.9; P6: 1523.7 versus 658.1; P7: 1225.6 versus 342.6 ms2)). BAL showed higher levels of epinephrine (P7: 100.5 versus 54 pg/mL), norepinephrine (P3: 221 versus 119.5; P4: 194 versus 130.5 pg/mL), adrenocorticotropic hormone (P2 10.5 versus 7.7; P5: 5.3 versus 3.6; P6: 10.9 versus 5.3; P7: 20.5 versus 7.1 pg/mL) and cortisol (P7: 6.9 versus 3.9 microg/dL). This indicates a higher sympathetic outflow using BAL versus TIVA during ear-nose-throat surgery.

Adrenocorticotropic Hormone↗

Comparison of esophageal Doppler, pulse contour analysis, and real-time pulmonary artery thermodilution for the continuous measurement of cardiac output.

OBJECTIVE: Continuous measurement of cardiac output (CCO) is of great importance in the critically ill. However, pulmonary artery thermodilution has been questioned for possible complications associated with right heart catheterization. Furthermore, measurements are delayed in the continuous mode during rapid hemodynamic changes. A new pulmonary artery catheter CCO device (Aortech, Bellshill, Scotland) enabling real-time update of cardiac output was compared with 2 different, less-invasive methods of CCO determination, esophageal Doppler and pulse contour analysis. DESIGN: Prospective, observational study. SETTING: University hospital, single institution. PARTICIPANTS: Patients scheduled for elective coronary artery bypass grafting (CABG). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: CCO measurements were analyzed using a Bland-Altman plot. Bias between CCO and pulse contour cardiac output (PCCO), and Doppler-derived cardiac output (UCCO) was (mean +/- 1 SD) -0.71 +/- 1 L/min versus -0.15 +/- 1.09 L/min, and between UCCO and PCCO -0.58 +/- 1.06 L/min. Bias was not significantly different among methods, nor were comparative values before and after cardiopulmonary bypass (p > 0.05). CONCLUSIONS: Agreement between the CCO method and both less-invasive measurements was clinically acceptable. There were no adverse events associated with the use of either device.

Aged↗

Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate.

BACKGROUND: The intravenous anesthetic etomidate exhibits structural similarities to specific alpha2-adrenoceptor agonists of the type such as dexmedetomidine. The current study was performed to elucidate the possible interaction of etomidate with alpha2-adrenoceptors in mice lacking individual alpha2-adrenoceptor subtypes (alpha2-KO). METHODS: Sedative and cardiovascular responses to etomidate and the alpha2-agonist, dexmedetomidine, were determined in mice deficient in alpha2-receptor subtypes. Inhibition of binding of the alpha2-receptor antagonist [3H]RX821002 to recombinant alpha2-receptors by etomidate was tested in human embryonic kidney (HEK293) cells in vitro. RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype. Intravenous injection of etomidate resulted in a transient increase (duration 2.4 +/- 0.2 min) in arterial blood pressure in wild-type mice (17 +/- 3 mmHg). Etomidate did not affect blood pressure in alpha2B-KO or alpha2AB-KO mice. In membranes from HEK293 cells transfected with alpha2-receptors, etomidate inhibited binding of the alpha2-antagonist, [3H]RX821002, with higher potency from alpha2B- and alpha2C-receptors than from alpha2A-receptors (Ki alpha2A 208 microm, alpha2B 26 microm, alpha2C 56 microm). In alpha2B-receptor-expressing HEK293 cells, etomidate rapidly increased phosphorylation of the extracellular signal-related kinases ERK1/2. CONCLUSIONS: These results indicate that etomidate acts as an agonist at alpha2-adrenoceptors, which appears in vivo primarily as an alpha2B-receptor-mediated increase in blood pressure. This effect of etomidate may contribute to the cardiovascular stability of patients after induction of anesthesia with etomidate.

Animals↗

Sedation and analgesia in the intensive care unit.

PURPOSE OF REVIEW: Sedation and analgesia are important means of providing care for the critically ill patient. RECENT FINDINGS: It is now clear that posttraumatic stress disorders resulting from an intensive care unit stay may be prevented by the right level of sedation. New drug developments but also recent findings in new ventilation strategies allow for a sedation management that is better tailored to an individual's need. Most importantly, regular definition of the appropriate level of sedation and analgesia as well as monitoring of the desired level will help to avoid over- and undersedation and may ultimately improve the outcome of the patient and reduce costs. SUMMARY: Sedation and analgesia are now regarded as an integral part of treatment on the intensive care unit instead of being an unpleasant but necessary and minor issue. The importance of monitoring the level of sedation and analgesia has only recently been realized. It remains to be shown that new management strategies including an evaluation of the patient, planned interventions and the choice of drugs will further improve the care for the critically ill.

Journal Article↗