Search PubMed⌕ Search

Biomedical subjects

G L Fraser

Publications and source records attributed to G L Fraser.

At least 19 recordsLinked to original sources
PubMed2001

Validating the Sedation-Agitation Scale with the Bispectral Index and Visual Analog Scale in adult ICU patients after cardiac surgery.

OBJECTIVE: To validate the Sedation-Agitation Scale (SAS) with the Visual Analog Scale (VAS) and Bispectral Index (BIS) in adult ICU patients after cardiac surgery. DESIGN: Prospective study comparing blinded evaluations of the SAS, VAS and BIS. SETTING: Forty-two-bed multidisciplinary ICU. PATIENTS AND PARTICIPANTS: Convenience sample of 39 adults after cardiac surgery. MEASUREMENTS AND RESULTS: Bispectral Index 3.2 was continuously recorded using the Aspect A-1000 and evaluators were blinded to this value. The bedside nurse and a trained researcher independently rated wakefulness using a 100 mm VAS upon patient arrival on the ICU, at first awakening, when ventilator weaning was started and after extubation; the researcher also evaluated patients using SAS. Upon arrival on the ICU, the median SAS score was 2 (interquartile range = 1-3), the mean VAS was 26+/-30 and the mean BIS was 70+/-16. Twenty-four patients underwent a trial of weaning from mechanical ventilation with a SAS of 4 (IQR = 4), VAS of 86+/-12 and BIS of 87+/-10. SAS correlated well with VAS performed by one researcher (r = 0.91, p < 0.001) or by 19 different bedside nurses (r = 0.43, p < 0.001) and with BIS 3.2 (r = 0.60, p < 0.001). The correlation between SAS and BIS was reduced in patients with above average electromyogram (EMG) power. As a measure of construct validity, significant differences were noted for the BIS, SAS, VAS and EMG between ICU arrival and extubation (all p < 0.001). CONCLUSIONS: Sedation-Agitation Scale and BIS are valid measures of wakefulness after cardiac surgery, but EMG interference may affect the accuracy of BIS for a small percentage of patients not receiving neuromuscular blockade.

Aged↗
PubMed2001

Monitoring sedation, agitation, analgesia, and delirium in critically ill adult patients.

The recent development of valid and reliable assessment tools to monitor agitation, sedation, analgesia, and delirium in the ICU represents an essential first step in the provision of patient comfort and the development of preferred treatment strategies. To make the ICU a more humane healing environment, these assessment tools must be used as part of a comprehensive evaluation of interventional and preventive treatments, pharmacologic and nonpharmacologic. In the spirit of the JCAHO, it may be time to add the evaluation of sedation, agitation, and delirium to that of pain assessment, making all aspects of patient comfort the fifth vital sign for the critically ill.

Adult↗
PubMed2001

Commentary. Balancing sedation and analgesia in the critically ill.

The authors have presented a template for a systematic approach to comforting critically ill patients that can be modified to suit institutional preferences. In this algorithm, the cause of patient discomfort is sought with the priority given to pain and then to anxiety. Special attention is directed to the identification of correctable causes of pain and anxiety with application of nonpharmacologic techniques or medications to control patient discomfort. This step is followed by subsequent reassessment of the need for sedation or anxiolysis and titration or discontinuation of therapy as able. The benefits of protocol-driven care are becoming increasingly evident, and the authors believe the algorithm outlined here provides a rational and practical approach to patient management. It also prompts the caregiver to reevaluate patients' needs and to keep to patients at target sedation levels. Doing so can promote cost effectiveness, reduce side effects caused by drugs, and decrease morbidity and ICU stay. Any treatment protocol or algorithm is simply a guide to therapy and cannot address every clinical situation. The importance of individualized care and physician or care team judgment must be emphasized.

Algorithms↗
PubMed2001

Monitoring sedation, agitation, analgesia, neuromuscular blockade, and delirium in adult ICU patients.

Preliminary evidence suggests that closely monitoring sedation may have a positive effect on patient outcomes, including reductions in intensive care unit (ICU) stay, duration of mechanical ventilatory support, and number of diagnostic tests requested to assess central nervous system function. In the last few years, subjective instruments to assess agitation and sedation have been developed and tested for reliability and validity, including the Sedation-Agitation Scale and the Motor Activity Assessment Scale. Similar efforts directed to delirium among ICU patients have produced several assessment tools to help clinicians with this difficult area of patient care. Promising techniques for objective assessment of sedation (such as the bispectral index) and strategies to guide neuromuscular blockade with train-of-four (TOF) or clinical exam monitoring have emerged. Future efforts should focus on evaluating the impact of these monitoring techniques on specific outcomes in an effort to improve patient comfort, minimize adverse events, and reduce resource consumption.

Journal Article↗
PubMed2001

Sedation assessment in critically ill adults.

OBJECTIVE: To review methods for assessing sedation in critically ill adults, discuss their impact on patient outcomes, and provide recommendations for implementing these methods into clinical practice in the intensive care unit (ICU). DATA SOURCES: A computerized search of MEDLINE from 1980 through June 2000 and a manual search of abstracts presented at recent critical care meetings were performed. STUDY SELECTION AND DATA EXTRACTION: Sedation assessment tools that have been used to titrate therapy in adult, critically ill patients were identified. Special emphasis was placed on sedation assessment instruments that have been prospectively validated. Objective methods that have been used to assess sedation therapy were also identified. DATA SYNTHESIS: Twenty-three adult sedation assessment instruments were identified. Few scales have been prospectively evaluated for validity (n = 6) or reliability (n = 7). Other methods of sedation assessment were identified (e.g., bispectral index monitor); however, most of these methods have only been studied in small subsets of critically ill patients. CONCLUSIONS: Incorporation of sedation assessment into ICU clinical practice may improve patient care. These sedation assessment instruments must be further evaluated to determine their impact on quality of care and ICU length of stay.

Adult↗
PubMed2001

The frequency and cost of patient-initiated device removal in the ICU.

OBJECTIVE: To determine the frequency and pattern with which patients in the intensive care unit (ICU) remove medical devices on their own, and the costs associated with this problem. DESIGN: Prospective observational study. SETTING: Two 10-bed sections of a multidisciplinary ICU in a tertiary care teaching hospital. PATIENTS: Adults admitted to the ICU for longer than 24 hours during October 1998. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Medical records were reviewed prospectively for the occurrence of patient-initiated device removal and the responses to those events by health care providers. Associated costs were estimated using hospital databases and Medicare physician reimbursement schedules. Annual cost estimates were calculated using 1997 admission statistics for 1211 adults in an ICU for more than 24 hours. Thirty-six patients were studied for 199 patient-days. Ten patients (28%) removed 42 devices: 88% of these events involved gastrointestinal tubes and vascular catheters. Significant agitation was documented within 2 hours before 74% of the events. Estimated cost associated with device removal was $7606, or $181/event. The estimated annual cost in this 42-bed ICU was more than $250,000. CONCLUSIONS: Patients commonly remove medical devices on their own, and this represents significant consumption of health care resources.

Aged↗
PubMed2000

The effects of delta agonists on locomotor activity in habituated and non-habituated rats.

The effects of the delta agonists SNC80 and deltorphin II on ambulation and rearing activity were measured in habituated and non-habituated rats. SNC80 (30, 100, 200, 400 nmol, i.c.v.) and deltorphin II (3, 15, 30, 60 nmol, i.c.v.) induced similar, dose-dependent biphasic locomotor effects in non-habituated subjects. An initial decrease in exploratory activity was associated with anxiogenic signs such as pilo-erection, freezing behaviour and pupil dilation for each drug. Pre-treatment with the delta antagonist naltrindole (10 nmol, i.c.v.) inhibited the depressant effect, but not the subsequent stimulant effect, on locomotor activity in response to 30 nmol deltorphin II in this assay (P<0.05). In habituated rats, deltorphin II (0.03, 0.1, 0.3, 3 nmol, i.c.v.) caused significant, naltrindole-reversible increases in locomotor activity (P<0.05 for all doses) at 1,000-fold lower doses than those required for a similar response to SNC80 (10, 30, 100, 300 nmol, i.c.v.). Pharmacokinetic studies suggest that these compounds penetrate the brain to similar extents following i.c.v. injection. The substantial potency difference between deltorphin II and SNC80 in stimulating locomotor activity in habituated rats suggests pharmacological heterogeneity for these delta opioid receptor agonists.

Animals↗
PubMed2000

Antihyperalgesic effects of delta opioid agonists in a rat model of chronic inflammation.

Opioid receptors in the brain activate descending pain pathways to inhibit the nociceptive response to acute noxious stimuli. The aim of the present study was to clarify the role of supraspinal opioid receptors in modulating the nociceptive response to persistent inflammation in rats. Subcutaneous administration of 50 microl of complete Freund's Adjuvant (CFA) into the plantar surface of the hindpaw induced a significant decrease in paw withdrawal latency to thermal stimuli (P<0.01) at 24 h post-injection. Intracerebroventricular (i.c.v.) administration of the mu opioid receptor agonists, DAMGO and morphine, and the delta opioid receptor agonists, deltorphin II and SNC80, significantly reversed the hyperalgesic response associated with peripheral inflammation in a dose-dependent manner (P<0.0001). The mu and delta agonists also significantly attenuated the antinociceptive response to acute thermal stimulation in rats (P<0.001). However, deltorphin II and SNC80 were less potent, and in the case of SNC80 less efficacious, in modulating the response to acute thermal nociception in comparison to hyperalgesia associated with persistent inflammation. These results indicate that mu and delta opioid receptors in the brain modulate descending pain pathways to attenuate the nociceptive response to acute thermal stimuli in both normal and inflamed tissues. The heightened response to delta agonists in the hyperalgesia model suggests that delta opioid receptors in the brain are promising targets for the treatment of pain arising from chronic inflammation.

Animals↗
PubMed2000

Antisense inhibition of delta-opioid receptor gene function in vivo by peptide nucleic acids.

Peptide nucleic acids (PNA) are synthetic analogs of DNA that hybridize to complementary oligonucleotide sequences with exceptional affinity and target specificity. The stability of PNA in biological fluids together with the unique hybridization characteristics of these structures suggests that PNA may have considerable potential as antisense agents for experimental use in vivo. To test this hypothesis, we attempted to modulate supraspinal delta-opioid receptor function in rats using PNA sequences designed to be complementary to a region of the rat delta-opioid receptor. Repeated i.c.v. administration of PNA over a period of 5 days significantly inhibited the antinociceptive response and locomotor response to selective delta-opioid receptor agonists. PNA attenuated delta-opioid receptor function in a sequence-specific, target-specific, and reversible manner characteristic of the functional inhibition caused by an antisense mechanism. There were no apparent toxicities arising from the PNA treatment based on the behavior of the animals and inspection of the treated tissues. Saturation binding studies on brain homogenates did not reveal any significant difference in receptor B(max) between treatment groups. However, [(35)S]guanosine-5'-O-(3-thio)triphosphate binding assays demonstrated a significant decrease in agonist efficacy in homogenates prepared from antisense-treated rats. Taken together, these results demonstrate that peptide nucleic acids are effective antisense agents in vivo and suggest that PNA may be a useful alternative to phosphodiester or phosphorothioate oligonucleotides, or variants thereof, for determination of gene function in vivo.

Analgesics↗
PubMed2000

Frequency, severity, and treatment of agitation in young versus elderly patients in the ICU.

STUDY OBJECTIVE: To study the frequency, duration, severity, and treatment of agitation in patients in the intensive care unit (ICU) to determine if the elderly represent a distinct population. DESIGN: Prospective cohort study SETTING: Tertiary care, 10-bed, multidisciplinary ICU. PATIENTS: All patients older than 18 years of age admitted for longer than 24 hours during a 4-month period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred thirty patients were studied for 916 patient-days; 63 (48%) were elderly (> 65 yrs). Nurses and physicians described agitated behavior in 92 patients (70.8%) during 534 (58.3%) patient-days, and it was severe or dangerous in 60 patients (46.1%) during 273 (30%) patient-days. There were no age-related differences in frequency, severity, and duration of agitation. Opiates, benzodiazepines, and haloperidol were administered during 72%, 62%, and 29% of agitated patient-days, respectively. Haloperidol was administered more often to elderly patients (p=0.015); otherwise no between-group differences were noted. Daily dosing requirements were less in the elderly for intermittent intravenous lorazepam, haloperidol, and morphine but not for midazolam (p=0.15). When these dosages were corrected for body mass, no statistical differences between young and old were found. CONCLUSION: In the ICU, the elderly are not a distinct population for agitation.

APACHE↗
PubMed2000

Supraspinal antinociceptive response to [D-Pen(2,5)]-enkephalin (DPDPE) is pharmacologically distinct from that to other delta-agonists in the rat.

The cloned delta-opioid receptor (DOR) is being investigated as a potential target for novel analgesics with an improved safety profile over mu-opioid receptor agonists such as morphine. The current study used antisense techniques to evaluate the role of DOR in mediating supraspinal antinociception in rats. All of the opioid agonists tested (delta-selective: deltorphin II, DPDPE, pCl-DPDPE, SNC80; mu-selective: DAMGO; i.c.v.) provided significant, dose-dependent antinociception in the paw pressure assay. Administration of a phosphodiester antisense oligonucleotide (i.c.v. ) targeted against DOR inhibited antinociception in response to SNC80, deltorphin II, and pCl-DPDPE compared with mismatch and saline-treated controls. However, antisense treatment did not inhibit the response to DPDPE or DAMGO. In contrast, the highly selective mu-antagonist CTOP blocked antinociception in response to ED(80) concentrations of DAMGO and DPDPE, reduced the response to pCl-DPDPE, and did not alter the response to deltorphin II or SNC80. In total, these data suggest that DOR mediates the antinociceptive response to deltorphin II, SNC80, and pCl-DPDPE at supraspinal sites and further demonstrates that the DOR-mediated response to deltorphin II and SNC80 is independent of mu-receptor activation. Conversely, supraspinal antinociception in response to DPDPE is mediated by a receptor distinct from DOR; this response is directly or indirectly sensitive to mu-receptor blockade. The distinct pharmacological profile of DPDPE suggests that either this prototypical delta-agonist mediates antinociception by a direct, nonselective interaction at mu-receptors or DPDPE interacts with a novel delta-subtype that, in turn, indirectly activates mu-receptors in the brain.

Analgesics, Opioid↗
PubMed1999

Characterization of [125I]AR-M100613, a high-affinity radioligand for delta opioid receptors.

AR-M100613 ([I]-Dmt-c[-D-Orn-2-Nal-D-Pro-D-Ala-]) is the iodinated analog of a cyclic casomorphin previously shown to be a potent antagonist at the delta opioid receptor. Specific [125I]AR-M100613 binding to rat whole brain membranes was saturable, reversible, and best fit to a one-site model (Kd = 0.080 +/- 0.008 nM, Bmax = 45.2 +/- 4.4 fmol/mg protein). [125I]AR-M100613 binding was displaced with high affinity by the delta opioid receptor ligands SNC-80, Deltorphin II and DPDPE but not the mu or kappa-selective receptor ligands DAMGO and U69593. Residual non-selective binding of [125I]AR-M 100613 to mu opioid receptors is blocked by the addition of CTOP to the assay buffer. [35S]GTPgammaS binding assays indicate that AR-M100613 is a potent, selective, and reversible antagonist for delta opioid receptors in rat brain membranes. The high-affinity, high specific activity, low nonspecific binding and antagonist profile of [125I]AR-M100613 favor its use as a radiochemical probe for delta opioid receptors.

Animals↗
PubMed1999

Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients.

OBJECTIVE: Subjective scales to assess agitation and sedation in adult intensive care unit (ICU) patients have rarely been tested for validity or reliability. We revised and prospectively tested the Sedation-Agitation Scale (SAS) for interrater reliability and compared it with the Ramsay scale and the Harris scale to test construct validity. DESIGN: A convenience sample of ICU patients was simultaneously and independently examined by pairs of trained evaluators by using the revised SAS, Ramsay, and Harris Scales. SETTING: Multidisciplinary 34-bed ICU in a nonuniversity, academic medical center. PATIENTS: Forty-five ICU patients (surgical and medical) were examined a total of 69 times by evaluator pairs. MEASUREMENTS AND MAIN RESULTS: The mean patient age was 63.2 yrs, 36% were female, and 71% were intubated. When classified by using SAS, 45% were anxious or agitated (SAS 5 to 7), 26% were calm (SAS 4), and 29% were sedated (SAS 1 to 3). Interrater correlation was high for SAS (r2 = .83; p < .001) and the weighted kappa score for interrater agreement was 0.92 (p < .001). Of 41 assessments scored as Ramsay 1, 49% scored SAS 6, 41% were SAS 5, 5% were SAS 4, and 2% each were SAS 3 or 7. SAS was highly correlated with the Ramsay (r2 = .83; p < .001) and Harris (r2 = .86; p < .001) scales. CONCLUSIONS: SAS is both reliable (high interrater agreement) and valid (high correlation with the Harris and Ramsay scales) in assessing agitation and sedation in adult ICU patients. SAS provides additional information by stratifying agitation into three categories (compared with one for the Ramsay scale) without sacrificing validity or reliability.

Adult↗
PubMed1999

Assessing sedation during intensive care unit mechanical ventilation with the Bispectral Index and the Sedation-Agitation Scale.

OBJECTIVE: To describe the level of sedation for a cohort of mechanically ventilated adult intensive care unit (ICU) patients using validated subjective and objective tools. DESIGN: Prospective convenience sample. SETTING: Multidisciplinary 34-bed ICU at Maine Medical Center, a 599-bed nonuniversity, academic medical center. PATIENTS: Sixty-three adult ICU patients were monitored during 64 episodes of ventilatory support. MEASUREMENTS AND MAIN RESULTS: Patients were prospectively evaluated by one trained investigator using the revised Sedation-Agitation Scale (SAS) and were simultaneously monitored for 1 to 5 hrs using the Bispectral Index (BIS), a numeric scale from 0 to 100 derived from the electroencephalogram. BIS values were assigned to baseline, stimulated, and average conditions for each patient by a separate investigator blinded to SAS scores. Ventilator settings, medications, and the lung injury severity (LIS) score were also recorded. Sedation levels varied from very deep sedation (SAS score = 1, BIS score = 43) to mild agitation (SAS score = 5, BIS score = 100). Heavily sedated patients (SAS score = 1-2, n = 20) had higher FIO2 (0.52 vs. 0.42, p = .008), oxygenation index (9.4 vs. 5.4, p = .03), and LIS scores (1.3 vs. 0.7, p = .004) and lower baseline (66 vs. 78, p = .01), average (66 vs. 81, p < .001), and stimulated (89 vs. 96, p = .016) BIS scores compared with more awake patients. Patients with intermittent neuromuscular blockade use (n = 4) had higher FIO2 (0.65 vs. 0.44, p = .006), minute ventilation (14.6 vs. 9.9 L/min, p = .005), positive end-expiratory pressure (7.5 vs. 4.8 cm H2O, p = .05), oxygenation index (15.7 vs. 6.0, p < .001), and LIS scores (3.3 vs. 1.0, p = .036) and were more sedated, with higher suppression ratios (3.5 vs. 0.6, p = .05) and lower SAS scores (1.5 vs. 4, p = .035). The average BIS values correlated well with SAS (r2 = .21, p < .001). CONCLUSIONS: SAS and BIS work well to describe the depth of sedation for ventilated ICU patients. Deeper sedation and intermittent neuromuscular blockade were used for patients with greater ventilatory requirements and more severe lung disease. The correlation between subjective and objective scales varied in medical, surgical, and trauma patients. Further research with SAS and BIS may facilitate the development of quantitative sedation guidelines for the ICU.

Adult↗
PubMed1998

Evidence for altered synthesis of type II collagen in patients with osteoarthritis.

There is evidence to suggest that the synthesis of type II collagen is increased in osteoarthritis (OA). Using an immunoassay, we show that the content of the C-propeptide of type II procollagen (CPII), released extracellularly from the newly synthesized molecule, is directly related to the synthesis of this molecule in healthy and osteoarthritic articular cartilages. In OA cartilage, CPII content is often markedly elevated (mean 7.6-fold), particularly in the mid and deep zones, reaching 29.6% of the content in newborn. Synthesis is also directly related to total collagen II content in OA, suggesting its importance in maintaining collagen content and cartilage structure. The release of CPII from cartilage is correlated directly with cartilage content. However, the increase in CPII in OA cartilage is not reflected in serum, where a significant reduction is observed. Together these studies provide evidence for alterations in procollagen II synthesis in vivo in patients with OA.

Adult↗
PubMed1997

Metabolism of haloperidol to pyridinium species in patients receiving high doses intravenously: is HPTP an intermediate?

The metabolism of haloperidol (HP) to the potentially neurotoxic pyridinium species, HPP+ and RHPP+, has been demonstrated in humans. In vitro studies in microsomes harvested from various animal species indicate that the tetrahydropyridines, HPTP and RHPTP, could be intermediates in this pathway. However, this has not yet been demonstrated in vivo in humans. In this study, plasma and urine collected from eight critically ill patients treated with high doses of intravenous HP were analyzed for HPTP and RHPTP using HPLC with electrochemical detection. However, neither HPTP nor RHPTP were detected despite plasma concentrations of HP and RHP higher than any previously reported. HPP+ and RHPP+ were both present in the urine in high concentrations and accounted for 1.1 +/- 0.5% and 5.3 +/- 3.6%, respectively, of the administered dose of HP. The apparent elimination half-lives of HPP+ and RHPP+ were 67.3 +/- 11.0 hr and 63.3 +/- 11.6 hr, respectively. The absence of HPTP and RHPTP in plasma and urine suggests that in humans these tetrahydropyridines either are insignificant intermediates in the metabolism of HP in vivo or are present only transiently at their site of formation and are not released into the circulation.

Adult↗