Tuhin K. Roy

A prospective trial of elective extubation in brain injured patients meeting extubation criteria for ventilatory support: A feasibility study

IntroductionTo assess the safety and feasibility of recruiting mechanically ventilated patients with brain injury who are solely intubated for airway protection and randomising them into early or delayed extubation, and to obtain estimates to refine sample-size calculations for a larger study. The design is a single-blinded block randomised controlled trial. A single large academic medical centre is the setting.MethodsSixteen neurologically stable but severely brain injured patients with a Glasgow Coma Score (GCS) of 8 or less were randomised to early or delayed extubation until their neurological examination improved. Eligible patients met standard respiratory criteria for extubation and passed a modified Airway Care Score (ACS) to ensure adequate control of respiratory secretions. The primary outcome measured between groups was the functional status of the patient at hospital discharge as measured by a Modified Rankin Score (MRS) and Functional Independence Measure (FIM). Secondary measurements included the number of nosocomial pneumonias and re-intubations, and intensive care unit (ICU) and hospital length of stay. Standard statistical assessments were employed for analysis.ResultsFive female and eleven male patients ranging in age from 30 to 93 years were enrolled. Aetiologies responsible for the neurological injury included six head traumas, three brain tumours, two intracerebral haemorrhages, two subarachnoid haemorrhages and three ischaemic strokes. There were no demographic differences between the groups. There were no unexpected deaths and no significant differences in secondary measures. The difference in means between the MRS and FIM were small (0.25 and 5.62, respectively). These results suggest that between 64 and 110 patients are needed in each treatment arm to detect a treatment effect with 80% power.ConclusionsRecruitment and randomisation of severely brain injured patients appears to be safe and feasible. A large multicentre trial will be needed to determine if stable, severely brain injured patients who meet respiratory and airway control criteria for extubation need to remain intubated.

Perioperative Statin Therapy and Renal Outcomes After Major Vascular Surgery: A Propensity-Based Analysis

OBJECTIVE To evaluate how the presence and timing of statin therapy affect perioperative renal outcomes after major vascular surgery. DESIGN Retrospective cohort study. SETTING Surgical intensive care unit at a single academic medical center. PARTICIPANTS Patients undergoing major vascular surgery between July 2004 and October 2005. MEASUREMENTS AND MAIN RESULTS The presence and timing of perioperative statin administration and the propensity for receiving such therapy were noted. Renal outcomes, lengths of stay, and mortality were reviewed. One hundred fifty-one procedures were performed. Eighty-nine patients (59%) received statin therapy. There was no evidence for renal protection with perioperative statin therapy (Delta creatinine 0.2 mg/dL v 0.2 mg/dL, p = 0.41; acute renal injury/acute renal failure 8% v 6%, p = 1.00; renal replacement therapy 3% v 3%, p = 1.00; all statin v no statin, respectively). With the possible exception of early reinstitution of statin therapy in chronic statin users, subgroup analyses failed to confirm an association between statin timing and prevention of postoperative renal dysfunction. CONCLUSIONS In the present investigation, neither the presence nor timing of perioperative statin therapy was associated with improved renal outcomes in patients undergoing a range of major vascular procedures. A possible exception is early postoperative reinitiation of statin therapy in chronic statin users. The discrepant results of available literature preclude a definitive statement on the use of statin therapy as a means of preventing postoperative renal dysfunction. An adequately powered prospective trial is needed before advocating the routine use of statin therapy for perioperative renal protection.

Capillary recruitment in a theoretical model for blood flow regulation in heterogeneous microvessel networks

In striated muscle, the number of capillaries containing moving red blood cells increases with increasing metabolic demand. This phenomenon, termed capillary recruitment, has long been recognized, but its mechanism has been unclear. Here, a theoretical model for metabolic blood flow regulation in a heterogeneous network is used to test the hypothesis that capillary recruitment occurs as a result of active control of arteriolar diameters, combined with unequal partition of hematocrit at diverging microvascular bifurcations. The network structure is derived from published observations of hamster cremaster muscle in control and dilated states. The model for modulation of arteriolar diameters includes length‐tension characteristics of vascular smooth muscle and responses of smooth muscle tone to myogenic, shear‐dependent, and metabolic stimuli. Blood flow is simulated including nonuniform hematocrit distribution. Convective and diffusive oxygen transport in the network is simulated. Oxygen‐dependent metabolic signals are assumed to be conducted upstream from distal vessels to arterioles. With increasing oxygen demand, arterioles dilate, blood flow increases, and the numbers of flowing arterioles and capillaries, as defined by red blood cell flux above a small threshold value, increase. Unequal hematocrit partition at diverging bifurcations contributes to recruitment and enhances tissue oxygenation. The results imply that capillary recruitment, as observed in the hamster cremaster preparations, can occur as a consequence of local control of arteriolar tone and the resulting nonuniform changes in red blood cell fluxes, and provide an explanation for observations of sequential recruitment of individual capillaries in response to modulation of terminal arteriolar diameter.

BiPAP in early Guillain-Barré syndrome may fail

BACKGROUND Non-invasive mechanical ventilation (BiPAP) has been introduced for use in neuromuscular respiratory disease such as amyotrophic lateral sclerosis and myasthenia gravis. There is no experience in Guillain-Barré syndrome. METHODS We describe for the first time the use of BiPAP to assist in the work of breathing in two consecutive patients with progressing Guillain-Barré syndrome (GBS) and marginal pulmonary function. RESULTS Our initial attempts to use BiPAP in GBS and early neuromuscular respiratory failure were totally unsuccessful. There was marked initial improvement; however, emergency intubation was needed in both patients, one of which became acutely cyanotic. CONCLUSIONS Until more experience is available, we strongly warn against using BiPAP in deteriorating patients with GBS.

Theoretical comparison of wall-derived and erythrocyte-derived mechanisms for metabolic flow regulation in heterogeneous microvascular networks

The objective of this study is to compare the effectiveness of metabolic signals derived from erythrocytes and derived from the vessel wall for regulating blood flow in heterogeneous microvascular networks. A theoretical model is used to simulate blood flow, mass transport, and vascular responses. The model accounts for myogenic, shear-dependent, and metabolic flow regulation. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. Arteriolar tone is assumed to depend on the conducted metabolic signal as well as local wall shear stress and wall tension, and arteriolar diameters are calculated based on vascular smooth muscle mechanics. The model shows that under certain conditions metabolic regulation based on wall-derived signals can be more effective in matching perfusion to local oxygen demand relative to regulation based on erythrocyte-derived signals, resulting in higher extraction and lower oxygen deficit. The lower effectiveness of the erythrocyte-derived signal is shown to result in part from the unequal partition of hematocrit at diverging bifurcations, such that low-flow vessels tend to receive a reduced hematocrit and thereby experience a reduced erythrocyte-derived metabolic signal. The model simulations predict that metabolic signals independent of erythrocytes may play an important role in local metabolic regulation of vascular tone and flow distribution in heterogeneous microvessel networks.

Prolonged coma from refractory status epilepticus

ObjectiveStatus epilepticus is a life-threatening medical condition. In its most severe form, refractory status epilepticus (RSE) seizures may not respond to first and second-line anti-epileptic drugs. RSE is associated with a high mortality and significant medical complications in survivors with prolonged hospitalizations.MethodsWe describe the clinical course of RSE in the setting of new onset lupus in a 31-year-old male who required prolonged barbiturate coma.ResultsSeizure stopped on day 64 of treatment. Prior to the resolution of seizures, discussion around withdrawal of care took place between the physicians and patients family. Medical care was continued because of the patients age, normal serial MRI studies, and the patients reversible medical condition.ConclusionFew evidence-based data exist to guide management of RSE. Our case emphasizes the need for continuous aggressive therapy when neuroimaging remains normal.

Functional sympatholysis and sympathetic escape in a theoretical model for blood flow regulation

A mathematical simulation of flow regulation in vascular networks is used to investigate the interaction between arteriolar vasoconstriction due to sympathetic nerve activity (SNA) and vasodilation due to increased oxygen demand. A network with 13 vessel segments in series is used, each segment representing a different size range of arterioles or venules. The network includes five actively regulating arteriolar segments with time-dependent diameters influenced by shear stress, wall tension, metabolic regulation, and SNA. Metabolic signals are assumed to be propagated upstream along vessel walls via a conducted response. The model exhibits functional sympatholysis, in which sympathetic vasoconstriction is partially abrogated by increases in metabolic demand, and sympathetic escape, in which SNA elicits an initial vasoconstriction followed by vasodilation. In accordance with experimental observations, these phenomena are more prominent in small arterioles than in larger arterioles when SNA is assumed to act equally on arterioles of all sizes. The results imply that a mechanism based on the competing effects on arteriolar tone of SNA and conducted metabolic signals can account for several observed characteristics of functional sympatholysis, including the different responses of large and small arterioles.

Theoretical analysis of the determinants of lung oxygen diffusing capacity

The process of pulmonary oxygen uptake is analyzed to obtain an explicit equation for lung oxygen diffusing capacity in terms of hematocrit and pulmonary capillary diameter. An axisymmetric model with discrete cylindrical erythrocytes is used to represent radial diffusion of oxygen from alveoli through the alveolar-capillary membrane into pulmonary capillaries, through the plasma, and into erythrocytes. Analysis of unsteady diffusion due to the passage of the erythrocytes shows that transport of oxygen through the alveolar-capillary membrane occurs mainly in the regions adjacent to erythrocytes, and that oxygen transport through regions adjacent to plasma gaps can be neglected. The model leads to an explicit formula for diffusing capacity as a function of geometric and oxygen transport parameters. For normal hematocrit and a capillary diameter of 6.75 μm, the predicted diffusing capacity is 102 ml O₂ min⁻¹ mmHg⁻¹. This value is 30-40% lower than values estimated previously by the morphometric method, which considers the total membrane area and the specific uptake rate of erythrocytes. Diffusing capacity is shown to increase with increasing hematocrit and decrease with increasing capillary diameter and increasing thickness of the membrane. Simulations of pulmonary oxygen uptake in humans under conditions of exercise or hypoxia based show closer agreement with experimental data than previous models, but still overestimate oxygen uptake. The remaining discrepancy may reflect effects of heterogeneity of perfusion and ventilation in the lung.

Acute Physiology and Chronic Health Evaluation (APACHE) III Outcome Prediction After Major Vascular Surgery

OBJECTIVE To investigate the performance of the Acute Physiology and Chronic Health Evaluation (APACHE) III scoring system in patients admitted to the intensive care unit (ICU) after major vascular surgery. DESIGN Retrospective cohort study. SETTING A tertiary referral center. PARTICIPANTS Three thousand one hundred forty-eight patients who underwent major vascular surgery between October 1994 and March 2006. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Data were abstracted from an institutional APACHE III database. Standardized mortality ratios (SMRs) (with 95% confidence intervals) were calculated. The area under the receiver operating characteristic curve (AUC) and Hosmer-Lemeshow C statistic were used to assess discrimination and calibration, respectively. The mean age of 3,148 patients studied was 70.5 years (+/- standard deviation 9.6). The mean Acute Physiology Score and the APACHE III score on the day of ICU admission were 31.0 (+/- 17.5) and 45.1 (+/- 18.8), respectively. The mean predicted ICU and hospital mortality rates were 3.2% (+/- 7.8%) and 5.0% (+/- 9.5%), respectively. The median (and interquartile range) ICU and hospital lengths of stay were 4.3 (3.6-5.1) and 14 days (11.9-16.8 days), respectively. The observed ICU mortality rate was 2.4% (75/3, 148 patients) and hospital mortality rate was 3.7% (116/3,148). The ICU and hospital SMRs were 0.74 (0.58-0.91) and 0.74 (0.61-0.88), respectively. The AUC of APACHE III-derived prediction of hospital mortality was 0.840 (95% confidence interval, 0.799-0.880), indicating excellent discrimination. The Hosmer-Lemeshow C statistic was 28.492, with a p value <0.01, indicating poor calibration. CONCLUSIONS The APACHE III scoring system discriminates well between survivors and nonsurvivors after major vascular surgery, but calibration of the model is poor.

Bayesian tracking of a nonlinear model of the capnogram.

Capnography, the monitoring of expired carbon dioxide (CO2 ) has been employed clinically as a non-invasive measure for the adequacy of ventilation of the alveoli of the lung. In combination with air flow measurements, the capnogram can be used to estimate the partial pressure of CO2 in the alveolar sacs. In addition, physiologically relevant parameters, such as the extent of CO2 rebreathing, the airway dead space, and the metabolic CO 2 production can be predicted. To calculate these parameters, mathematical models have been previously formulated and applied to experimental data using off-line optimization procedures. Unfortunately, this does not permit online identification of the capnogram to detect changes in the physiological model parameters. In the present study, a Bayesian method for breath-by-breath identification of the volumetric capnogram is presented. The method integrates a model of CO2 exchange in the lungs, which is nonlinear due to the nature of human tidal breathing, with a particle filtering algorithm for estimation of the model parameters and changes therein. In addition, this allowed for a dynamic prediction of the unmeasured alveolar CO2 tension. The method is demonstrated using simulations of the capnogram. The proposed method could aid the clinician in the interpretation of the capnogram