David B. MacLeod

Dexmedetomidine pharmacodynamics: Part II: Crossover comparison of the analgesic effect of dexmedetomidine and remifentanil in healthy volunteers.

Background:Dexmedetomidine is a highly selective &agr;2-adrenoceptor agonist used for short-term sedation of mechanically ventilated patients. The analgesic profile of dexmedetomidine has not been fully characterized in humans. Methods:This study was designed to compare the analgesic responses of six healthy male volunteers during stepwise target-controlled infusions of remifentanil and dexmedetomidine. A computer-controlled thermode was used to deliver painful heat stimuli to the volar side of the forearms of the subjects. Six sequential 5-s stimuli (ranging from 41° to 50°C) were delivered in random order. The recorded visual analog scale was used to fit an Emax model. Results:Compared to baseline, remifentanil infusions resulted in a right shift of the sigmoid curve (increased T50, the temperature producing a visual analog scale score of 50% of the maximal effect, from 46.1°C at baseline to 48.4° and 49.1°C during remifentanil infusions) without a change of the steepness of the curve (identical Hill coefficients &ggr; during baseline and remifentanil). Compared to baseline, dexmedetomidine infusions resulted in both a right shift of the sigmoid curve (increased T50 to 47.2°C) and a decrease in the steepness of the curve (decreased &ggr; from 3.24 during baseline and remifentanil infusions to 2.45 during dexmedetomidine infusions). There was no difference in the pain responses between baseline and after recovery from remifentanil infusions (identical T50 and &ggr;). Conclusion:As expected, dexmedetomidine is not as effective an analgesic as the opioid remifentanil. The difference in the quality of the analgesia with remifentanil may be a reflection of a different mechanism of action or a consequence of the sedative effect of dexmedetomidine.

Regional brain blood flow in man during acute changes in arterial blood gases

•  The partial pressures of arterial carbon dioxide () and oxygen () has a marked influence on brain blood flow. •  It is unclear if the larger brain arteries are also sensitive to changing and and if different areas of the brain possess different sensitivities. •  We separately altered and and measured the diameter and blood flow in the main arteries delivering blood to the cortex and brainstem. •  During alterations in and , the large arteries changed diameter and blood flow to the brainstem changed more than that to the cortex. •  These findings change the basis of our understanding of brain blood flow control in humans.

Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.

Background and Objectives Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. Case Report Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 μg/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with β-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. Conclusions Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients.

The desaturation response time of finger pulse oximeters during mild hypothermia

Pulse oximeters may delay displaying the correct oxygen saturation during the onset of hypoxia. We investigated the desaturation response times of pulse oximeter sensors (forehead, ear and finger) during vasoconstriction due to mild hypothermia and vasodilation caused by glyceryl trinitrate. Ten healthy male volunteers were given three hypoxic challenges of 3 min duration under differing experimental conditions. Mild hypothermia increased the mean response time of finger oximeters from 130 to 215 s. Glyceryl trinitrate partly offset this effect by reducing the response time from 215 to 187 s. In contrast, the response times of the forehead and ear oximeters were unaffected by mild hypothermia, but the difference between head and finger oximeters was highly significant (p < 0.0001). The results suggest that the head oximeters provide a better monitoring site for pulse oximeters during mild hypothermia.

A New Teaching Model for Resident Training in Regional Anesthesia

The adequacy of resident education in regional anesthesia is of national concern. A teaching model to improve resident training in regional anesthesia was instituted in the Anesthesiology Residency in 1996 at Duke University Health System. The key feature of the model was the use of a CA-3 resident in the preoperative area to perform regional anesthesia techniques. We assessed the success of the new model by comparing the data supplied by the Anesthesiology Residency to the Residency Review Committee for Anesthesiology for the training period July 1992–June 1995 (pre-model) and the training period July 1998–June 2001 (post-model). During the 3-yr training period, the pre-model CA-3 residents (n = 12) performed a cumulative total of 80 (58–105) peripheral nerve blocks (PNBs), 66 (59–74) spinal anesthetics, and 133 (127–142) epidural anesthetics. The CA-3 post-model residents (n = 10) performed 350 (237–408) PNBs, 107 (92–123) spinal anesthetics, and 233 (221–241) epidural anesthetics (P < 0.0001). All results are reported as median (interquartile range). We conclude that our new teaching model using our CA-3 residents as block residents in the preoperative area has increased their clinical exposure to PNBs.

Regional cerebral blood flow in humans at high altitude: gradual ascent and 2 wk at 5,050 m

The interindividual variation in ventilatory acclimatization to high altitude is likely reflected in variability in the cerebrovascular responses to high altitude, particularly between brain regions displaying disparate hypoxic sensitivity. We assessed regional differences in cerebral blood flow (CBF) measured with Duplex ultrasound of the left internal carotid and vertebral arteries. End-tidal Pco2, oxyhemoglobin saturation (SpO2), blood pressure, and heart rate were measured during a trekking ascent to, and during the first 2 wk at, 5,050 m. Transcranial color-coded Duplex ultrasound (TCCD) was employed to measure flow and diameter of the middle cerebral artery (MCA). Measures were collected at 344 m (TCCD-baseline), 1,338 m (CBF-baseline), 3,440 m, and 4,371 m. Following arrival to 5,050 m, regional CBF was measured every 12 h during the first 3 days, once at 5-9 days, and once at 12-16 days. Total CBF was calculated as twice the sum of internal carotid and vertebral flow and increased steadily with ascent, reaching a maximum of 842 ± 110 ml/min (+53 ± 7.6% vs. 1,338 m; mean ± SE) at ∼ 60 h after arrival at 5,050 m. These changes returned to +15 ± 12% after 12-16 days at 5,050 m and were related to changes in SpO2 (R(2) = 0.36; P < 0.0001). TCCD-measured MCA flow paralleled the temporal changes in total CBF. Dilation of the MCA was sustained on days 2 (+12.6 ± 4.6%) and 8 (+12.9 ± 2.9%) after arrival at 5,050 m. We observed no significant differences in regional CBF at any time point. In conclusion, the variability in CBF during ascent and acclimatization is related to ventilatory acclimatization, as reflected in changes in SpO2.

Regulation of brain blood flow and oxygen delivery in elite breath-hold divers

The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and cardiorespiratory metrics were measured during maximum dry apneas in elite breath-hold divers (n=17). To isolate the effects of apnea and IBM from the concurrent changes on ABG, end-tidal forcing (‘clamp’) was then used to replicate an identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23  to 37 mm Hg (30±7 mm Hg). Elevation in mean arterial pressure was greater during apnea than during clamp reaching +54±24% versus 34±26%, respectively; however, CBF increased similarly between apnea and clamp (93.6±28% and 83.4±38%, respectively). This latter observation indicates that during the overall apnea period IBM per se do not augment CBF and that the brain remains sufficiently protected against hypertension. Termination of apnea was not determined by reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial oxygen content, oxygen delivery was maintained by commensurately increased CBF.

The Accuracy of a Near-Infrared Spectroscopy Cerebral Oximetry Device and Its Potential Value for Estimating Jugular Venous Oxygen Saturation

BACKGROUND:An intriguing potential clinical use of cerebral oximeter measurements (SctO2) is the ability to noninvasively estimate jugular bulb venous oxygen saturation (SjvO2). Our purpose in this study was to determine the accuracy of the FORE-SIGHT® (CAS Medical Systems, Branford, CT), which is calibrated to a weighted average of 70% (SjvO2) and 30% arterial saturation, for Food and Drug Administration pre-market approval 510(k) certification by adapting an industry standard protocol, ISO 9919:2005 (www.ISO.org) (used for pulse oximeters), and to evaluate the use of SctO2 and SpO2 measurements to noninvasively estimate jugular venous oxygen saturation (SnvO2). METHODS:Paired blood gas samples from the radial artery and the jugular venous bulb were collected from 20 healthy volunteers undergoing progressive oxygen desaturation from 100% to 70%. The blood sample pairs were analyzed via co-oximetry and used to calculate the approximate mixed vascular cerebral blood oxygen saturation, or reference SctO2 values (refSctO2), during increasing hypoxia. These reference values were compared to bilateral FORE-SIGHT SctO2 values recorded simultaneously with the blood gas draws to determine its accuracy. Bilateral SctO2 and SpO2 measurements were then used to calculate SnvO2 values which were compared to SjvO2. RESULTS:Two hundred forty-six arterial and 253 venous samples from 18 subjects were used in the analysis. The ipsilateral FORE-SIGHT SctO2 values showed a tolerance interval (TI) of [−10.72 to 10.90] and Lin concordance correlation coefficient (CCC) with standard error (SE) of 0.83 ± 0.073 with the refSctO2 values calculated using arterial and venous blood gases. The ipsilateral data had a CCC of 0.81 + 0.059 with TI of [−9.22 to 9.40] with overall bias of 0.09%, and amplitude of the root mean square of error after it was corrected with random effects analysis was 2.92%. The bias and variability values between the ipsilateral and the contralateral FORE-SIGHT SctO2 measurements varied from person to person. The SnvO2 calculated from the ipsilateral SctO2 and SpO2 data showed a CCC ± SE of 0.79 ± 0.088, TI = [−14.93 to 15.33], slope of 0.98, y-intercept of 1.14% with SjvO2 values with a bias of 0.20% and an Arms of 4.08%. The SnvO2 values calculated independently from contralateral forehead FORE-SIGHT SctO2 values were not as correlated with the SjvO2 values (contralateral side CCC + SE = 0.72 ± 0.118, TI = [−14.86 to 15.20], slope of 0.66, and y-intercept of 20.36%). CONCLUSIONS:The FORE-SIGHT cerebral oximeter was able to estimate oxygen saturation within the tissues of the frontal lobe under conditions of normocapnia and varying degrees of hypoxia (with 95% confidence interval of [−5.60 to 5.78] with ipsilateral blood sample data). These findings from healthy volunteers also suggest that the use of the calculated SnvO2 derived from SctO2 and SpO2 values may be a reasonable noninvasive method of estimating SjvO2 and therefore global cerebral oxygen consumption in the clinical setting. Further laboratory and clinical research is required to define the clinical utility of near-infrared spectroscopy determination of SctO2 and SnvO2 in the operating room setting.

Influence of high altitude on cerebral blood flow and fuel utilization during exercise and recovery

This study assessed the dynamic response of global cerebral blood flow (CBF) and cerebral fuel utilization during and following incremental supine exercise to exhaustion. Global CBF increased more during exercise and recovery at high altitude (HA) compared with sea level (SL) such that cerebral oxygen delivery ( CDO2 ) was maintained. The increase in cerebral metabolic rate of oxygen during maximal exercise at HA was half the increase observed at SL. Arterial lactate production during exercise at the same absolute intensities was greater at HA compared with SL, but reduced at the same relative intensities. Cerebral carbohydrate uptake (lactate and glucose) is greater than oxygen uptake at HA compared with SL, indicating a shift towards an increased non‐oxidative metabolic utilization. These results suggest that CBF increases to maintain CDO2 during exercise at HA while changes in arterial lactate concentration and exercise intensity augment the oxidative and non‐oxidative pathways to cerebral metabolism at HA.

Individual-Specific, Beat-to-beat Trending of Significant Human Blood Loss: The Compensatory Reserve.

ABSTRACT Current monitoring technologies are unable to detect early, compensatory changes that are associated with significant blood loss. We previously introduced a novel algorithm to calculate the Compensatory Reserve Index (CRI) based on the analysis of arterial waveform features obtained from photoplethysmogram recordings. In the present study, we hypothesized that the CRI would provide greater sensitivity and specificity to detect blood loss compared with traditional vital signs and other hemodynamic measures. Continuous noninvasive vital sign waveform data, including CRI, photoplethysmogram, heart rate, blood pressures, SpO2, cardiac output, and stroke volume, were analyzed from 20 subjects before, during, and after an average controlled voluntary hemorrhage of ∼1.2 L of blood. Compensatory Reserve Index decreased by 33% in a linear fashion across progressive blood volume loss, with no clinically significant alterations in vital signs. The receiver operating characteristic area under the curve for the CRI was 0.90, with a sensitivity of 0.80 and specificity of 0.76. In comparison, blood pressures, heart rate, SpO2, cardiac output, and stroke volume had significantly lower receiver operating characteristic area under the curve values and specificities for detecting the same volume of blood loss. Consistent with our hypothesis, CRI detected blood loss and restoration with significantly greater specificity than did other traditional physiologic measures. Single measurement of CRI may enable more accurate triage, whereas CRI monitoring may allow for earlier detection of casualty deterioration.