Biomedical subjects

Arun K Gupta

Publications and source records attributed to Arun K Gupta.

31 records · Page 2Linked to original sources

PubMed2004

Diffusion limited oxygen delivery following head injury.

OBJECTIVE: To use a range of techniques to explore diffusion limitation as a mechanism of cellular hypoxia in the setting of head injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Thirteen patients within 7 days of closed head injury underwent imaging studies. Tissue for ultrastructural studies was obtained from a cohort of seven patients who required surgery. INTERVENTIONS: Cerebral tissue PO2 (PtO2) was obtained using a multiple-variable sensor, and images of oxygen extraction fraction (OEF), derived from positron emission tomography, were used to calculate cerebral venous PO2 (PvO2). These data were used to derive the PvO2-PtO2 gradient in a region of interest around the sensor, which provided a measure of the efficiency of microvascular oxygen delivery. Measurements were repeated after PaCO2 was reduced from 37 +/- 3 to 29 +/- 3 torr (4.9 +/- 0.4 to 3.9 +/- 0.4 kPa) to assess the ability of the microvasculature to increase oxygen unloading during hypocapnia-induced hypoperfusion. Pericontusional tissue was submitted to electron microscopy to illustrate the structural correlates of physiologic findings. MEASUREMENTS AND MAIN RESULTS: Tissue regions with hypoxic levels of PtO2 (<10 torr) had similar levels of PvO2 compared with nonhypoxic areas and hence displayed larger PvO2-PtO2 gradients (27 +/- 2 vs. 9 +/- 8 torr, p <.001). Despite similar cerebral blood flow reductions with hyperventilation, hypoxic regions achieved significantly smaller OEF increases compared with normoxic regions (7 +/- 5 vs. 16 +/- 6 %, p <.05). Pericontusional tissue showed varying degrees of endothelial swelling, microvascular collapse, and perivascular edema. CONCLUSIONS: Increased diffusion barriers may reduce cellular oxygen delivery following head injury and attenuate the ability of the brain to increase oxygen extraction in response to hypoperfusion. Global or regional OEF underestimates tissue hypoxia due to such mechanisms.

Adolescent↗

PubMed2004

Hyperglycemia and brain tissue pH after traumatic brain injury.

OBJECTIVE: Hyperglycemia occurring after head injury is associated with poor neurological outcome. We tested the hypothesis that blood glucose levels are associated with brain tissue pH (pH(b)) and that the correction of hyperglycemia would result in an improvement in pH(b). METHODS: This is a retrospective analysis of a prospectively collected database. Thirty-four patients in a tertiary care neuroscience critical care unit with major traumatic brain injury underwent pH(b) monitoring. RESULTS: A total of 428 glucose measurements were recorded during pH(b) monitoring. Mean glucose level was 7.1 mmol/L (range, 2.8-21.7 mmol/L) and median (interquartile range) pH(b) was 7.11 mmol/L (7.00-7.19 mmol/L). To account for the correlated, unbalanced nature of the data, a linear generalized estimating equation model was created. This model predicted that for each 1 mmol/L increase in blood glucose, pH(b) changed by -0.011 mmol/L (95% confidence interval, -0.016 to -0.005 mmol/L; P < 0.001). This relationship remained significant in a multivariable model that included cerebral perfusion pressure, brain tissue oxygen and carbon dioxide tension, and brain temperature. Twenty-one episodes of significant hyperglycemia (>or=11.1 mmol/L) treated with intravenous insulin were identified. Insulin therapy significantly reduced blood glucose concentration from a median (interquartile range) of 11.9 mmol/L (range, 11.4-13.6 mmol/L) to 8.8 mmol/L (range, 7.3-9.6 mmol/L; P < 0.001). Baseline pH(b) was not significantly different from pH(b) associated with the subsequent glucose reading of less than 11.1 mmol/L (P = 0.29), but there was a suggestion of improvement if the change in blood glucose was large. CONCLUSION: Blood glucose is associated with brain tissue acidosis in patients with major head injury. Prospective studies are required to confirm these results and to determine whether treatment of hyperglycemia improves outcome.

Adolescent↗

PubMed2003

Pharmacokinetics and pharmacodynamics of dopamine and norepinephrine in critically ill head-injured patients.

OBJECTIVE: To explore the pharmacokinetics and pharmacodynamics of dopamine and norepinephrine. DESIGN: Prospective, controlled, trial. SETTING: Neurosciences critical care unit. PATIENTS: Eight patients with a head injury, requiring dopamine or norepinephrine infusions to support cerebral perfusion pressure (CPP). INTERVENTION: Patients received in randomised order, either dopamine or norepinephrine to achieve and maintain a CPP of 70 mmHg, and then, following a 30-min period of stable haemodynamics, a CPP of 90 mmHg. Data were then acquired using the second agent. Haemodynamic measurements were made during each period and a blood sample was obtained at the end of each study period for analysis of plasma catecholamine concentrations MEASUREMENTS AND RESULTS: Plasma levels of norepinephrine and dopamine were significantly related to infusion rates but did not have a simple linear relationship to haemodynamic parameters. However, there was a significant quadratic relationship between the infusion rate of dopamine and cardiac index (r2=0.431), and systemic vascular resistance index (r2=0.605), with a breakpoint (at which cardiac index reduced and SVRI increased) at a dopamine plasma level of approximately 50 nM/l (corresponding to an infusion rate of approximately 15 microg.kg(-1).min(-1)). CONCLUSIONS: Norepinephrine and dopamine have predictable pharmacokinetics; however, those of dopamine do not fit a simple first-order kinetic model. The pharmacodynamic effects of dopamine and norepinephrine show much inter-individual variability and unpredictability. Plasma levels of dopamine appear to relate to variations in adrenergic receptor effects with break points that reflect expectations from infusion-rate related pharmacodynamics.

Adult↗

PubMed2003

Non-neurological organ dysfunction in neurocritical care.

PURPOSE: To determine the incidence of non-neurological organ dysfunction in patients with severe neurological injury. MATERIALS AND METHODS: Modified daily SOFA (mSOFA) scores were retrospectively calculated for 55 consecutive patients with severe head injury or subarachnoid hemorrhage. mSOFA was defined as the sum of the 5 non-neurological component SOFA scores, maximum mSOFA as the sum of the most abnormal non-neurological SOFA component scores and delta mSOFA as the difference between maximum mSOFA and admission mSOFA. Organ failure was defined as a SOFA component score > or =3. RESULTS: Median (IQR) admission, maximum and delta mSOFA scores were 4 (3-6), 8 (6-9), and 2 (1-5), respectively. Respiratory and cardiac failure developed in 80% and 82% of patients, respectively. No patient developed renal or hepatic failure. Three patients developed hematological failure. There was no difference between survivors and nonsurvivors with respect to admission mSOFA (P =.45), maximum mSOFA (P =.54), or delta mSOFA (P =.19). There was no difference between those patients with favorable or unfavorable neurological outcome with respect to admission mSOFA (P =.24), maximum mSOFA (P =.84), or delta mSOFA (P =.20). CONCLUSIONS: Cardiopulmonary failure, as defined by SOFA, is common in intensive care unit patients with severe head injury and subarachnoid hemorrhage. In contrast to other intensive care unit patient populations, the mortality of patients with closed head injury or subarachnoid hemorrhage was not related to the severity of organ dysfunction on admission or its development during the intensive care unit stay.

Adult↗

PubMed2003

Role of plasma renin activity in the management of primary vesicoureteric reflux: a preliminary report.

BACKGROUND: Nonoperative management is the choice of therapy in most patients with primary vesicoureteric reflux (VUR). Such patients are regularly monitored for breakthrough urinary tract infection, deterioration of renal function, and progression/ appearance of new scars as the indicators for switching over to surgical intervention. In this descriptive study, we report our additional observations on serial measurement of plasma renin activity (PRA) in a group of such children followed prospectively. METHODS: Twenty-six children (16 males and 10 females) with various grades (grades I to V) of primary VUR were enrolled. Besides the conventional investigations, we also monitored PRA. Ureteric reimplantation was performed based on established international criteria. PRA levels were correlated with the need for surgical intervention retrospectively. RESULTS: Mean age at presentation was 39.3 months (range, 12 to 120 months). Nineteen children (73%) were subjected to ureteric reimplantation. The mean PRA in this group (N = 19) was 6.97 ng/mL/hour versus 3.28 ng/mL/hour in patients who were continued on nonoperative management (N = 7). Postoperatively, the PRA reduced and stabilized in all 18 patients at a mean value of 5.4 ng/mL/hour. CONCLUSION: The currently accepted end points of medical management are inconsistent. On the other hand, 94.7% of children in the surgical group had shown an activation and a progressive increase in PRA. Postoperatively, the PRA was reduced and stabilized in all these patients. Our preliminary observations suggest that high PRA is a more sensitive indicator for surgical intervention as compared to the existing criteria.

Adolescent↗

PubMed2003

The effects of large-dose propofol on cerebrovascular pressure autoregulation in head-injured patients.

UNLABELLED: In healthy individuals, cerebrovascular pressure autoregulation is preserved or even improved when propofol is infused. We examined the effect of an increase in propofol plasma concentration on pressure autoregulation in 10 head-injured patients. Using target-controlled infusions, the static rate of autoregulation was determined at a moderate (2.3 +/- 0.4 microg/mL) and a large (4.3 +/- 0.04 microg/mL) plasma target concentration of propofol. Using norepinephrine to control cerebral perfusion pressure, transcranial Doppler measurements from the middle cerebral artery were made at a cerebral perfusion pressure of 70 and 85 mm Hg at each propofol concentration. Middle cerebral artery flow velocities at the large propofol concentration were significantly lower than at the moderate concentration, without any concurrent increase in arterio-jugular difference in oxygen content, a finding compatible with maintained flow-metabolism coupling. Despite this, static rate of autoregulation decreased significantly from 54% +/- 36% to 28% +/- 35% (P = 0.029). Our data suggest that after head injury, the cerebrovascular effects of propofol are different from those observed in healthy individuals. We propose that large doses of propofol should be used cautiously in head-injured patients, because there is the potential to increase the injured brain's vulnerability to secondary insults. IMPLICATIONS: Propofol is used for sedation and control of intracranial pressure in head-injured patients. In contrast to previous data from healthy individuals, we show a deterioration of cerebrovascular pressure autoregulation with fast propofol infusion rates after head injury. Large propofol doses may increase the injured brain's vulnerability to secondary insults.

Adult↗

PubMed2002

Effect of hyperventilation on cerebral blood flow in traumatic head injury: clinical relevance and monitoring correlates.

OBJECTIVE: To investigate the effect of hyperventilation on cerebral blood flow in traumatic brain injury. DESIGN: A prospective interventional study. SETTING: A specialist neurocritical care unit. PATIENTS: Fourteen healthy volunteers and 33 patients within 7 days of closed head injury. INTERVENTIONS: All subjects underwent positron emission tomography imaging of cerebral blood flow. In patients, PaCO2 was reduced from 36 +/- 1 to 29 +/- 1 torr (4.8 +/- 0.1 to 3.9 +/- 0.1 kPa) and measurements repeated. Jugular venous saturation (SjvO2 ) and arteriovenous oxygen content differences (AVDO2 ) were monitored in 25 patients and values related to positron emission tomography variables. MEASUREMENTS AND MAIN RESULTS: The volumes of critically hypoperfused and hyperperfused brain (HypoBV and HyperBV, in milliliters) were calculated based on thresholds of 10 and 55 mL.100g(-1).min(-1), respectively. Whereas baseline HypoBV was significantly higher in patients ( p<.05), baseline HyperBV was similar to values in healthy volunteers. Hyperventilation resulted in increases in cerebral perfusion pressure (p <.0001) and reductions in intracranial pressure (p <.001), whereas SjvO2 (>50%) and AVDO2 (<9 mL/mL) did not exceed global ischemic thresholds. However, despite these beneficial effects, hyperventilation shifted the cerebral blood flow distribution curve toward the hypoperfused range, with a decrease in global cerebral blood flow (31 +/- 1 to 23 +/- 1 mL.100g(-1).min(-1); p<.0001) and an increase in HypoBV (22 [1-141] to 51 [2-428] mL; p<.0001). Hyperventilation-induced increases in HypoBV were apparently nonlinear, with a threshold value between 34 and 38 torr (4.5-5 kPa). CONCLUSIONS: Hyperventilation increases the volume of severely hypoperfused tissue within the injured brain, despite improvements in cerebral perfusion pressure and intracranial pressure. Significant hyperperfusion is uncommon, even at a time when conventional clinical management includes a role for modest hyperventilation. These reductions in regional cerebral perfusion are not associated with ischemia, as defined by global monitors of oxygenation, but may represent regions of potentially ischemic brain tissue.

Adolescent↗

PubMed2002

Correlation between cerebral blood flow, substrate delivery, and metabolism in head injury: a combined microdialysis and triple oxygen positron emission tomography study.

Microdialysis continuously monitors the chemistry of a small focal volume of the cerebral extracellular space. Conversely, positron emission tomography (PET) establishes metabolism of the whole brain, but only for the duration of the scan. The objective of this study was to apply both techniques to head-injured patients simultaneously to assess the relation between microdialysis (glucose, lactate, lactate/pyruvate [L/P] ratio, and glutamate) and PET (cerebral blood flow [CBF], cerebral blood volume, oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen) parameters. Microdialysis catheters were inserted into the frontal cerebral cortex and adipose tissue of the anterior abdominal wall of 17 severely head-injured patients. Microdialysis was performed during PET scans, with regions of interest defined by the location of the microdialysis catheter membrane. An intervention (hyperventilation) was performed in 13 patients. The results showed that combining PET and microdialysis to monitor metabolism in ventilated patients is feasible and safe, although logistically complex. There was a significant relation between the L/P ratio and the OEF (Spearman r = 0.69, P = 0.002). There was no significant relation between CBF and the microdialysis parameters. Moderate short-term hyperventilation appeared to be tolerated in terms of brain chemistry, although no areas were sampled by microdialysis where the OEF exceeded 70%. Hyperventilation causing a reduction of the arterial carbon dioxide tension by 0.9 kPa resulted in a significant elevation of the OEF, in association with a reduction in glucose, but no significant elevation in the L/P ratio or glutamate.

Adolescent↗

PubMed2002

Adverse cerebral events detected after subarachnoid hemorrhage using brain oxygen and microdialysis probes.

OBJECTIVE: A prospective observational study was conducted to investigate whether episodes of ischemia are detected by continuous cerebral monitoring and whether such episodes are related to clinical outcome. METHODS: Forty patients (35 after subarachnoid hemorrhage and 5 after complex aneurysm surgery) were monitored for a total of 174 days (mean, 4 d; range, 1-12 d). Brain tissue partial pressures of oxygen and carbon dioxide, pH, and temperature were measured continuously using Neurotrend sensors (Codman, Bracknell, England). Bedside analysis of extracellular chemistry was performed hourly using microdialysis. Glasgow Outcome Scale score was assessed at 3 to 6 months. RESULTS: Patients with poor World Federation of Neurosurgical Societies grades (4 and 5) or an unfavorable outcome (severe disability or death) had, on average, higher lactate and lactate/pyruvate ratio but lower glucose/lactate ratio (P < or = 0.05). Brain tissue partial pressure of oxygen decreased to below 1.1 kPa in 78% of the patients for 18% (95% confidence interval, 12-24%) of time monitored. There were 197 episodes in which brain tissue partial pressures of oxygen decreased to below 1.1 kPa for at least 30 minutes. Unfavorable outcome was associated with more of these episodes (8.8 episodes; 95% confidence interval, 4.4-13.2 episodes) than favorable outcome (2.2 episodes; 95% confidence interval, 1.1-3.3 episodes), as well as an episode of glutamate levels of more than 10 micromol/L or lactate/pyruvate ratio more than 40 (P < 0.05, chi(2) test). CONCLUSION: Intraparenchymal oximetry and microdialysis can detect but fail to predict the development of delayed cerebral ischemia. There were associations between episodes of low brain oxygen, abnormal microdialysis, and unfavorable outcome, but these associations were weak.

Brain↗

PubMed2002

Advanced monitoring in the neurology intensive care unit: microdialysis.

Cerebral microdialysis is a relatively new technique for measuring the levels of brain extracellular chemicals, which to date has predominantly been used as a research tool. This review considers the technical aspects of microdialysis, the importance of the commonly measured chemicals, and the use of microdialysis to monitor patients with ischemic stroke, head injury, and subarachnoid hemorrhage. The advantages and disadvantages of microdialysis are discussed, as is its future potential.

Brain Chemistry↗

PubMed2002

Measurement of brain tissue oxygenation performed using positron emission tomography scanning to validate a novel monitoring method.

OBJECT: The benefits of measuring cerebral oxygenation in patients with brain injury are well accepted; however, jugular bulb oximetry, which is currently the most popular monitoring technique used has several shortcomings. The goal of this study was to validate the use of a new multiparameter sensor that measures brain tissue oxygenation and metabolism (Neurotrend) by comparing it with positron emission tomography (PET) scanning. METHODS: A Neurotrend sensor was inserted into the frontal region of the brain in 19 patients admitted to the neurointensive care unit. After a period of stabilization, the patients were transferred to the PET scanner suite where C15O, 15O2, and H2(15)O PET scans were obtained to facilitate calculation of regional cerebral blood volume, O2 metabolism, blood flow, and O2 extraction fraction (OEF). Patients were given hyperventilation therapy to decrease arterial CO2 by approximately 1 kPa (7.5 mm Hg) and the same sequence of PET scans was repeated. For each scanning sequence, end-capillary O2 tension (PvO2) was calculated from the OEF and compared with the reading of brain tissue O2 pressure (PbO2) provided by the sensor. In three patients the sensor was inserted into areas of contusion and these patients were eliminated from the analysis. In the subset of 16 patients in whom the sensor was placed in healthy brain, no correlation was found between the absolute values of PbO2 and PvO2 (r = 0.2, p = 0.29); however a significant correlation was obtained between the change in PbO2 (deltaPbO2) and the change in PvO2 (deltaPvO2) produced by hyperventilation in a 20-mm region of interest around the sensor (p = 0.78, p = 0.0035). CONCLUSIONS: The lack of correlation between the absolute values of PbO2 and PvO2 indicates that PbO2 cannot be used as a substitute for PvO2. Nevertheless, the positive correlation between deltaPbO2 and deltaPvO2 when the sensor had been inserted into healthy brain suggests that tissue PO2 monitoring may provide a useful tool to assess the effect of therapeutic interventions in brain injury.

Adult↗

PubMed2002

Cerebral oxygen and microdialysis monitoring during aneurysm surgery: effects of blood pressure, cerebrospinal fluid drainage, and temporary clipping on infarction.

OBJECT: The aim of this study was to investigate potential episodes of cerebral ischemia during surgery for large and complicated aneurysms, by examining the effects of arterial temporary clipping and the impact of confounding variables such as blood pressure and cerebrospinal fluid (CSF) drainage. METHODS: Brain tissue PO2, PCO2, and pH, as well as temperature and extracellular glucose, lactate, pyruvate, and glutamate were monitored in 46 patients by using multiparameter sensors and microdialysis. Baseline data showed that brain tissue PO2 decreased significantly, below a mean arterial pressure (MAP) threshold of 70 mm Hg. Further evidence of its relationship with cerebral perfusion pressure was shown by an increase in mean brain tissue PO2 after drainage of CSF from the basal cisterns (Wilcoxon test, p < 0.01). Temporary clipping was required in 31 patients, with a mean total duration of 14 minutes (range 3-52 minutes), causing brain tissue PO2 to decrease and brain tissue PCO2 to increase (Wilcoxon test, p < 0.01). In patients in whom no subsequent infarction developed in the monitored region, brain tissue PO2 fell to 11 mm Hg (95% confidence interval 8-14 mm Hg). A brain tissue PO2 level below 8 mm Hg for 30 minutes was associated with infarction in any region (p < 0.05 according to the Fisher exact test); other parameters were not predictive of infarction. Intermittent occlusions of less than 30 minutes in total had little effect on extracellular chemistry. Large glutamate increases were only seen in two patients, in both of whom brain tissue PO2 during occlusion was continuously lower than 8 mm Hg for longer than 38 minutes. CONCLUSIONS: The brain tissue PO2 decreases with hypotension, and, when it is below 8 mm Hg for longer than 30 minutes during temporary clipping, it is associated with increasing extracellular glutamate levels and cerebral infarction.

Adult↗

PubMed2002

Long-acting GnRH analogue triptorelin therapy in central isosexual precocious puberty.

OBJECTIVE: To evaluate the efficacy of long acting GnRH analogue in improving the auxological outcome of patients with central isosexual precocious puberty (CIPP) and to determine the factors influencing the response. METHODS: Thirty-five patients (30 girls, 5 boys) with CIPP were treated with a long acting GnRH analogue, triptorelin. Final height outcomes and factors affecting treatment were analyzed. RESULTS: Treatment was started at the chronological age (CA) of 6.5 1.8 years in girls and 4.4 1.5 years in boys and continued for a period of 3.7 1.8 years in girls and 6 1.8 years in boys. Follow-up period after discontinuation of treatment was 2.2 0.5 years in girls and 2.6 0.3 years in boys. Treatment led to regression of precocious puberty and reversal of secondary sexual characteristics. There was decline in growth rate reflected by a fall in heightSD of 0.8 0.8 in girls and 2.3 0.9 in boys (p = 0.014), an even greater retardation in bone age (BA) advancement with a decrease in BA-CA of 1.7 1 years in girls and 2.7 1 years in boys and a fall in heightSDBA of 1.5 1.1 in girls and 2.1 1.6 in boys. Final height (149.8 6.9 cm in girls and 161.9 3.9 cm in boys) exceeded projected height at the onset of treatment (143.4 8.3 cm in girls and 154.3 2.7 cm in boys) by 6.4 2.4 cm in girls and 7.6 1.5 cm in boys ( p < 0.001 in both the groups). Factors influencing height gain included age at start of therapy (r = 0.715), BA-CA at the time of initiation of treatment (r = 0.734), heightSDBA at the onset of treatment ( r = 0.566) and the duration of treatment (r = 0.711). Girls treated at an age of less than 6 years (n = 9) had a greater height gain (8.7 1.6 cm versus 5.3 1.9 cm, p < 0.001) and achieved similar final height (148.7 8 cm versus 150.2 6.6 cm) in those treated after this age (n = 21). No side effects of GnRH therapy were observed in the study. CONCLUSION: Long acting GnRH therapy is effective in improving the auxological outcome of patients with CIPP. Maximum benefit is observed in girls with greater bone age advancement treated at a younger age and for a longer duration of treatment. These girls had lower bone age advance at discontinuation of treatment.

Child↗