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Christopher M Bernards

Publications and source records attributed to Christopher M Bernards.

13 recordsLinked to original sources
PubMed2006

Concurrent expansion of plasma volume and left ventricular end-diastolic volume in patients after rapid infusion of 5% albumin and lactated Ringer's solution.

STUDY OBJECTIVE: To examine the effects of plasma volume expansion on plasma volume, left ventricular end-diastolic volume (LVEDV), and cardiac index (CI) after rapid fluid infusion, as knowledge of the degree of concordance between plasma and cardiac preload expansion could optimize LVEDV expansion without administering excessive fluid. DESIGN: Randomized, double-blinded study. SETTING: Academic community hospital. PATIENTS: 20 patients undergoing elective coronary artery bypass surgery. INTERVENTIONS: Patients were administered either 5% albumin (5 mL/kg) or lactated Ringer's solution (25 mL/kg) over 30 minutes, just before incision. MEASUREMENTS: Serial measurements of plasma volume, LVEDV by transesophageal echocardiography, and CI were recorded. MAIN RESULTS: Albumin expanded plasma volume and LVEDV to a similar degree (11.3% and 13.2%). In contrast, lactated Ringer's solution increased plasma volume more than LVEDV (21.7% vs 14.4%; P = 0.0005). Increased LVEDV significantly but poorly correlated with increased CI (r(2) = 0.2, P < 0.0001) for both fluids. However, LVEDV expansion was brief and returned to baseline or less within 30 minutes for both fluids despite continued plasma volume expansion and increased CI. Correspondingly, rates of decline from peak expansion were significantly faster for LVEDV than plasma volume expansion for both albumin (-1.9% + 1.9%/min vs -0.1% + 0.1%/min; P = 0.0008) and lactated Ringer's (-1.1% + 0.8%/min vs -0.4% + 0.2%/min; P = 0.006). CONCLUSIONS: Intravenous fluids increased LVEDV to a lesser extent and duration than did plasma volume expansion. Monitoring of LVEDV was a poor guide for fluid administration to maximize CI.

Aged↗
PubMed2006

Cerebrospinal fluid and spinal cord distribution of baclofen and bupivacaine during slow intrathecal infusion in pigs.

BACKGROUND: Increasing numbers of patients are receiving chronic intrathecal infusions of local anesthetics, baclofen, opioids, and other analgesics via implanted pumps. These infusions typically deliver drugs at rates measured in microliters per hour. However, to date, there have been no studies aimed at characterizing drug distribution within cerebrospinal fluid (CSF) and spinal cord during these slow infusion rates. Therefore, this study was designed to address this knowledge gap. METHODS: Anesthetized pigs were instrumented with eight intrathecal microdialysis probes placed at multiple points along the neuroaxis in both the anterior and posterior intrathecal space to permit continuous CSF sampling for measurement of bupivacaine and baclofen concentrations. Animals were divided into three groups and received bupivacaine and baclofen infusions at 20 or 1,000 microl/h or as a 1,000-microl bolus over 5 min every hour. Drug administration continued for 8 h, at which time the animals were killed, and the spinal cord was removed and divided into 1-cm-long sections that were further divided into anterior and posterior portions for measurement of bupivacaine and baclofen concentrations. RESULTS: In all groups, drug concentration in CSF and spinal cord decreased rapidly as a function of distance from the site of administration, with most drug found within a few centimeters. In addition, there were significant anterior-posterior differences in both CSF and spinal cord drug concentrations. CONCLUSIONS: During slow intrathecal infusion, drug distribution in CSF and spinal cord is severely limited in all groups, although significantly more so in the 20-microl/h infusion group.

Animals↗
PubMed2004

Pharmacokinetics of intrathecal oligodeoxynucleotides.

BACKGROUND: Intrathecal administration of antisense oligonucleotides is a frequently used technique to alter gene expression for research purposes. However, in the future, antisense oligonucleotides will likely be administered intrathecally to humans for therapeutic purposes. To date, there have been no systematic studies of the pharmacokinetics of intrathecal oligonucleotides. This study was designed to fill that knowledge gap. METHODS: Microdialysis probes were placed intrathecally at the L4, L1, and T11 vertebral levels and epidurally at the L4 vertebral level in pigs. One of the study oligodeoxynucleotides (10-, 18-, or 30-nucleotide-long sequences of the human MDR-1 gene) was injected intrathecally at the L4 level at time 0. Microdialysis samples were obtained for measurement of oligodeoxynucleotide samples at 5-min intervals until 20 min, 10-min intervals until 60 min, and 20-min intervals until 180 min. Noncompartmental pharmacokinetic analysis was performed using PK Solutions software. RESULTS: Mean residence time and terminal elimination half-life did not differ significantly among the three oligodeoxynucleotides at any sampling site. In contrast, area under the concentration-time curve differed significantly among the oligodeoxynucleotides at all sampling sites and was inversely related to oligodeoxynucleotide length at the L4 and L1 intrathecal sites but not the T11 or epidural sampling sites. Similarly, clearance and volumes of distribution at the L4 level differed significantly among the oligodeoxynucleotides and were directly related to oligodeoxynucleotide length. CONCLUSION: The intrathecal pharmacokinetics of oligodeoxynucleotides are largely determined by oligodeoxynucleotide length. This contrasts with smaller drug molecules, such as opioids, for which intrathecal and epidural pharmacokinetics are largely determined by lipid solubility, not size. The potential clinical utility of this information is that oligodeoxynucleotide distribution within the central nervous system may be controllable to some degree by varying oligodeoxynucleotide length.

Animals↗
PubMed2004

Recent insights into the pharmacokinetics of spinal opioids and the relevance to opioid selection.

PURPOSE OF REVIEW: Spinal opioid administration was introduced into clinical practice nearly 25 years ago in the hope of producing intense spinal analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. While spinal opioid administration can clearly be an effective analgesic technique, there is a widespread misconception that any opioid administered epidurally or intrathecally will produce analgesia by a selective spinal mechanism. This is simply not true; multiple opioids that are commonly administered spinally produce analgesia by uptake into the systemic circulation with subsequent redistribution to brainstem opioid receptors. In an effort to help clinicians understand why some opioids are not suitable for selective spinal analgesia, this review describes recent insights into the fate of intrathecally and epidurally administered opioids. RECENT FINDINGS: A series of animal studies published over the last 4 or more years have provided the first measurements of opioid concentration in the epidural space, intrathecal space, spinal cord and peri-spinal tissues following intrathecal and epidural opioid administration. These studies characterize, for the first time, the factors governing the rate and extent to which different opioids redistribute from the epidural and intrathecal spaces to reach target opioid receptors in the spinal cord dorsal horn. The findings indicate that increasing lipid solubility decreases the spinal cord bioavailability of spinally administered opioids. SUMMARY: These animal data help to explain multiple clinical studies that have demonstrated that the analgesic effect of spinally administered lipid-soluble opioids is due in part, if not exclusively, to uptake into plasma and distribution to brainstem opioid receptors.

Journal Article↗
PubMed2003

Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids.

BACKGROUND: The pharmacokinetics of epidurally administered drugs has been the subject of many studies, yet drug concentration in the epidural space has never been measured. This study was undertaken to characterize the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids on the basis of measurement of drug concentration in each of these compartments after epidural administration. METHODS: Morphine plus alfentanil, fentanyl, or sufentanil were administered epidurally in anesthetized pigs. Microdialysis was used to sample the epidural space and the cerebrospinal fluid for measurement of opioid concentration over time. Plasma samples were obtained from the central venous plasma and the epidural venous plasma. These data were used to calculate relevant pharmacokinetic parameters, including mean residence time, elimination half-lives, areas under the concentration versus time curves, clearance, and volume of distribution for each opioid in each compartment. RESULTS: Some of the more important findings were that the cerebrospinal fluid and plasma pharmacokinetics of the opioids did not parallel their epidural pharmacokinetics and that their hydrophobic character governed multiple aspects of their lumbar epidural pharmacokinetics. CONCLUSIONS: The findings indicate that the spinal pharmacokinetics of these drugs are complex and, in some ways, counterintuitive. Also, the bioavailability of opioids in the cerebrospinal fluid and epidural space is determined primarily by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.

Adipose Tissue↗
PubMed2003

Epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidural opioids (part 2): effect of epinephrine.

BACKGROUND: The ability of epinephrine to improve the efficacy of epidurally administered drugs is assumed to result from local vasoconstriction and a consequent decrease in drug clearance. However, because drug concentration in the epidural space has never been measured, our understanding of the effect of epinephrine on epidural pharmacokinetics is incomplete. This study was designed to characterize the effect of epinephrine on the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids. METHODS: Morphine plus alfentanil, fentanyl, or sufentanil was administered epidurally with and without epinephrine (1:200,000) to pigs. Opioid concentration was subsequently measured in the epidural space, central venous plasma, and epidural venous plasma, and these data were used to calculate relevant pharmacokinetic parameters. RESULTS: The pharmacokinetic effects of epinephrine varied by opioid and by sampling site. For example, in the lumbar epidural space, epinephrine increased the mean residence time of morphine but decreased that of fentanyl and sufentanil. Epinephrine had no effect on the terminal elimination half-life of morphine in the epidural space, but it decreased that of fentanyl and sufentanil. In contrast, in the lumbar intrathecal space, epinephrine had no effect on the pharmacokinetics of alfentanil, fentanyl, or sufentanil, but it increased the area under the concentration-time curve of morphine and decreased its elimination half-life. CONCLUSIONS: The findings indicate that the effects of epinephrine on the spinal pharmacokinetics of these opioids are complex and often antithetical across compartments and opioids. In addition, the data clearly indicate that the pharmacokinetic effects of epinephrine in spinal "compartments" cannot be predicted from measurements of drug concentration in plasma, as has been assumed for decades.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2003

A model to evaluate the pharmacokinetic and pharmacodynamic variables of extended-release products using in vivo tissue microdialysis in humans: bupivacaine-loaded microcapsules.

UNLABELLED: Biodegradable microcapsules produce an ultra-long duration of local anesthesia. We hypothesized that this duration is caused by the sustained-release of bupivacaine from the microcapsules into the surrounding tissue. Previous studies investigated the pharmacokinetics (PKs) of bupivacaine after release from microcapsules and absorption into the systemic circulation. Microdialysis sampling can determine the PKs of any drug at its site of injection. This study was performed to characterize the PKs of bupivacaine and dexamethasone released from microcapsules at a subcutaneous injection site over a 96-h period in volunteers. Bupivacaine concentrations were compared with clinical variables of local anesthetic blockade. This study demonstrates that bupivacaine is released in a sustained manner from microcapsules, that bupivacaine concentrations increase for 24-34 h after microcapsule injection, and that analgesia parallels the tissue bupivacaine concentration obtained by microdialysis. Analgesia was equally rapid in onset with aqueous and microcapsule bupivacaine (P = 0.23). Analgesia was still present at 78% of microcapsule-injected sites after 96 h, significantly longer than for aqueous bupivacaine (P < 0.001). Mild pruritus was the most common side effect, occurring with 56% of the microcapsule injections. Dexamethasone-containing bupivacaine microcapsules are well tolerated and produce a prolonged duration of skin analgesia. Systemic absorption of bupivacaine produces higher peak plasma levels after aqueous injection than after microcapsule injection, despite the injection of a threefold larger load of bupivacaine in the latter. IMPLICATIONS: Microcapsules loaded with bupivacaine and dexamethasone and administered by subcutaneous injection produce prolonged cutaneous anesthesia and analgesia. Determination of local tissue pharmacokinetic variables of bupivacaine by microdialysis confirms that the prolonged duration of anesthesia is caused by the extended release characteristics of the microcapsules.

Adult↗
PubMed2002

Understanding the physiology and pharmacology of epidural and intrathecal opioids.

Epidural and intrathecal opioid administration has become an important part of contemporary medical practice in a variety of clinical settings. It has been widely assumed that any opioid placed in the epidural or intrathecal spaces will produce highly selective spinally mediated analgesia that is superior to that produced by other analgesic techniques. Unfortunately, this is simply not true. In fact, multiple opioids are currently employed for spinal use despite the fact that clinical evidence has shown that spinal administration does not produce analgesia with a selective spinal mechanism or that the analgesia produced is not superior to that produced by intravenous administration. This chapter presents the basic science and clinical data available to assist clinicians in identifying which opioids are appropriate for spinal use and which are not.

Analgesia, Epidural↗
PubMed2002

Chronic cocaine exposure alters carbon dioxide reactivity but does not affect cerebral blood flow autoregulation in anesthetized dogs.

BACKGROUND: Cocaine use is common in trauma victims. Consequently, understanding how cocaine alters normal physiology is important to providing appropriate medical care for these patients. This study was designed to identify how chronic cocaine exposure alters cerebrovascular physiology. METHODS: Ten dogs (seven experimental, three control) were studied. Transcranial Doppler was used to measure CO2 reactivity and autoregulation of cerebral blood flow velocity (CBFvel). Measurements were made in anesthetized animals (0.6% or 1.8% isoflurane in oxygen and intravenous fentanyl) at baseline before cocaine exposure and then at weekly intervals for 4 weeks. During the 4-week study period, cocaine was administered intravenously four times per day. RESULTS: Cocaine did not alter autoregulation of CBFvel in response to changes in mean arterial pressure. However, cocaine markedly impaired CO2 reactivity in three of the seven animals. In this subset of animals, increasing Paco2 decreased CBFvel, which is consistent with vasoconstriction rather than vasodilation. CONCLUSION: Chronic cocaine exposure does not alter autoregulation of CBFvel but does alter CO2 reactivity in a subset of susceptible animals. If confirmed in humans, these findings have implications for traumatic brain injury patients who are chronic cocaine users. Specifically, the findings suggest that hyperventilation could exacerbate intracranial hypertension in a subset of these patients.

Anesthesia, General↗