Iain Haitsma

Safety and efficacy of frameless and frame-based intracranial biopsy techniques

SummaryBackground. Frameless stereotaxy or neuronavigation has evolved into a feasible technology to acquire intracaranial biopsies with good accuracy and little mortality. However, few studies have evaluated the diagnostic yield, morbidity, and mortality of this technique as compared to the established standard of frame-based stereotactic brain biopsy. We report our experience of a large number of procedures performed with one or other technique. Patients and methods. We retrospectively assessed 465 consecutive biopsies done over a ten-year time span; Data from 391 biopsies (227 frame-based and 164 frameless) were available for analysis. Patient demographics, peri-operative characteristics, and histological diagnosis were reviewed and then information was analysed to identify factors associated with the biopsy not yielding a diagnosis and of it being followed by death. Results. On average, nine tissue samples were taken with either stereotaxy technique. Overall, the biopsy led to a diagnosis on 89.4% of occasions. No differences were found between the two biopsy procedures. In a multiple regression analysis, it was found that left-sided lesions were less likely to result in a non-diagnostic tissue sample (p = 0.023), and cerebellar lesions showed a high risk of negative histology (p = 0.006). Postoperative complications were seen after 12.1% of biopsies, including 15 symptomatic haemorrhages (3.8%). There was not a difference between the rates of complication after either a frame-based or a frameless biopsy. Overall, peri-operative complications (p = 0.030) and deep-seated lesions (p = 0.060) increased the risk of biopsy-related death. Symptomatic haemorrhages resulting in death (1.5% of all biopsies) were more frequently seen after biopsy of a fronto-temporally located lesion (p = 0.007) and in patients with a histologically confirmed lymphoma (p = 0.039). Conclusions. The diagnostic yield, complication rates, and biopsy-related mortality did not differ between a frameless biopsy technique and the established frame-based technique. The site of the lesion and the occurrence of a peri-operative complication were associated with the likelihood of failure to achieve a diagnosis and with death after biopsy. We believe that using intraoperative frozen section or cytologic smear histology is essential during a stereotactic biopsy in order to increase the diagnostic yield and to limit the number of biopsy specimens that need to be taken.

Advanced monitoring in the intensive care unit: brain tissue oxygen tension.

Cerebral monitoring of patients with acute intracranial disorders generally focuses on intracranial pressure and cerebral perfusion pressure monitoring. Over the past few years, several new techniques have become available for more detailed routine monitoring of cerebral oxygenation and metabolism. Brain tissue oxygen pressure measurement is increasingly being used for evaluation of cerebral oxygenation. This article discusses brain tissue oxygen pressure measurement in regards to its technical aspects, safety, reliability, and value relative to other techniques for evaluation of cerebral oxygenation. Published experimental and clinical data are considered, and the current status of the clinical use and indications of the technique are summarized. Monitoring may be performed in relatively undamaged parts of the brain or, preferably, in the penumbra region of an intracerebral lesion. Pathophysiologic evidence warrants targeting therapy for patients with traumatic brain injury and subarachnoid hemorrhage toward improvement of cerebral oxygenation guided by continuous monitoring of brain tissue oxygen tension.

Towards improving the safety and diagnostic yield of stereotactic biopsy in a single centre

BackgroundPreviously, we reported on our single centre results regarding the diagnostic yield of stereotactic needle biopsies of brain lesions. The yield then (1996–2006) was 89.4%. In the present study, we review and evaluate our experience with intraoperative frozen-section histopathologic diagnosis on-demand in order to improve the diagnostic yield.MethodsOne hundred sixty-four consecutive frameless biopsy procedures in 160 patients (group 1, 2006–2010) were compared with the historic control group (group 2, n = 164 frameless biopsy procedures). Diagnostic yield, as well as demographics, morbidity and mortality, was compared. Statistical analysis was performed by Students t, Mann–Whitney U, Chi-square test and backward logistic regression when appropriate.ResultsDemographics were comparable. In group 1, a non-diagnostic tissue specimen was obtained in 1.8%, compared to 11.0% in group 2 (p = 0.001). Also, both the operating time and the number of biopsies needed were decreased significantly. Procedure-related mortality decreased from 3.7% to 0.6% (p = 0.121). Multivariate analysis only proved operating time (odds ratio (OR), 1.012; 95% confidence interval (CI), 1.000–1.025; p = 0.043), a right-sided lesion (OR, 3.183; 95% CI, 1.217–8.322; p = 0.018) and on-demand intraoperative histology (OR, 0.175; 95% CI, 0.050–0.618; p = 0.007) important factors predicting non-diagnostic biopsies.ConclusionsThe importance of a reliable pathological diagnosis as obtained by biopsy must not be underestimated. We believe that when performing stereotactic biopsy for intracranial lesions, next to minimising morbidity, one should strive for as high a positive yield as possible. In the present single centre retrospective series, we have shown that using a standardised procedure and careful on-demand intraoperative frozen-section analysis can improve the diagnostic yield of stereotactic brain biopsy procedures as compared to a historical series.

The new licox combined brain tissue oxygen and brain temperature monitor: Assessment of in vitro accuracy and clinical experience in severe traumatic brain injury

OBJECTIVE Monitoring of brain tissue oxygen tension is increasingly being used to monitor patients after severe traumatic brain injury and to guide therapies aimed at maintaining brain tissue oxygen tension above threshold levels. The new Licox PMO combined oxygen and temperature catheter (Integra LifeSciences, Plainsboro, NJ) combines measurements of oxygen tension and temperature in a single probe inserted through a bolt mechanism. In this study, we sought to evaluate the accuracy of the new Licox PMO probe under controlled laboratory conditions and to assess the accuracy of oxygen tension and temperature measurements and the new automated card calibration system. We also describe our clinical experience with the Licox PMO probe. METHODS Oxygen tension was measured in a 2-chambered apparatus at different oxygen tensions and temperatures. The new card calibration system was compared with a manually calibrated system. Rates of hematoma, infection, and dislodgement in our clinical experience were recorded. RESULTS The new Licox PMO probe accurately measures oxygen tension over a wide range of oxygen concentrations and physiological temperatures, but it does have a small tendency to underestimate oxygen tension (mean error, −3.8 ± 3.5%) that is more pronounced between the temperatures of 33 and 39°C. The thermistor of the PMO probe also has a tendency to underestimate temperature when compared with a resistance thermometer (mean error, −0.67 ± 0.22°C). The card calibration system was also found to introduce some variability in measurements of oxygen tension when compared with a manually calibrated system. Clinical experience with the new probe indicates good placement within the white matter using the improved bolt system and low rates of hematoma (2.9%), infection (0%), and dislodgement (5.9%). conclusion The new Licox PMO probe is accurate but has a small, consistent tendency to under-read oxygen tension that is more pronounced at higher temperatures. The probe tends to under-read temperature by 0.5 to 0.8°C across temperatures, suggesting that caution should be used when brain temperature is measured with the Licox PMO probe and used to guide temperature-directed treatment strategies. The Licox PMO probe improves upon previous models in allowing consistent and accurate placement in the white matter and obviating the need for placement of 2 separate probes to measure oxygen tension and temperature.

Factors influencing intracranial pressure monitoring guideline compliance and outcome after severe traumatic brain injury.

Objective:To determine adherence to Brain Trauma Foundation guidelines for intracranial pressure monitoring after severe traumatic brain injury, to investigate if characteristics of patients treated according to guidelines (ICP+) differ from those who were not (ICP-), and whether guideline compliance is related to 6-month outcome. Design:Observational multicenter study. Patients:Consecutive severe traumatic brain injury patients (≥16 yrs, n = 265) meeting criteria for intracranial pressure monitoring. Measurements and Main Results:Data on demographics, injury severity, computed tomography findings, and patient management were registered. The Glasgow Outcome Scale Extended was dichotomized into death (Glasgow Outcome Scale Extended = 1) and unfavorable outcome (Glasgow Outcome Scale Extended 1–4). Guideline compliance was 46%. Differences between the monitored and nonmonitored patients included a younger age (median 44 vs. 53 yrs), more abnormal pupillary reactions (52% vs. 32%), and more intracranial pathology (subarachnoid hemorrhage 62% vs. 44%; intraparenchymal lesions 65% vs. 46%) in the ICP+ group. Patients with a total intracranial lesion volume of ~150 mL and a midline shift of ~12 mm were most likely to receive an intracranial pressure monitor and probabilities decreased with smaller and larger lesions and shifts. Furthermore, compliance was low in patients with no (Traumatic Coma Databank score I −10%) visible intracranial pathology. Differences in case-mix resulted in higher a priori probabilities of dying (median 0.51 vs. 0.35, p < .001) and unfavorable outcome (median 0.79 vs. 0.63, p < .001) in the ICP+ group. After correction for baseline and clinical characteristics with a propensity score, intracranial pressure monitoring guideline compliance was not associated with mortality (odds ratio 0.93, 95% confidence interval 0.47–1.85, p = .83) nor with unfavorable outcome (odds ratio 1.81, 95% confidence interval 0.88–3.73, p = .11). Conclusions:Guideline noncompliance was most prominent in patients with minor or very large computed tomography abnormalities. Intracranial pressure monitoring was not associated with 6-month outcome, but multiple baseline differences between monitored and nonmonitored patients underline the complex nature of examining the effect of intracranial pressure monitoring in observational studies.

Multicenter Evaluation of the Course of Coagulopathy in Patients with Isolated Traumatic Brain Injury: Relation to CT Characteristics and Outcome

This prospective multicenter study investigated the association of the course of coagulation abnormalities with initial computed tomography (CT) characteristics and outcome in patients with isolated traumatic brain injury (TBI). Patient demographics, coagulation parameters, CT characteristics, and outcome data of moderate and severe TBI patients without major extracranial injuries were prospectively collected. Coagulopathy was defined as absent, early but temporary, delayed, or early and sustained. Delayed/sustained coagulopathy was associated with a higher incidence of disturbed pupillary responses (40% versus 27%; p<0.001) and higher Traumatic Coma Data Bank (TCDB) CT classification (5 (2-5) versus 2 (1-5); p=0.003) than in patients without or with early, but short-lasting coagulopathy. The initial CT of patients with delayed/sustained coagulopathy more frequently showed intracranial hemorrhage and signs of raised intracranial pressure (ICP) compared to patients with early coagulopathy only. This was paralleled by higher in-hospital mortality rates (51% versus 33%; p<0.05), and poorer 6-month functional outcome in patients with delayed/sustained coagulopathy. The relative risk for in-hospital mortality was particularly related to disturbed pupillary responses (OR 8.19; 95% CI 3.15,21.32; p<0.001), early, short-lasting coagulopathy (OR 6.70; 95% CI 1.74,25.78; p=0.006), or delayed/sustained coagulopathy (OR 5.25; 95% CI 2.06,13.40; p=0.001). Delayed/sustained coagulopathy is more frequently associated with CT abnormalities and unfavorable outcome at 6 months after TBI than early, short-lasting coagulopathy. Our finding that not only the mere presence but also the time course of coagulopathy holds predictive value for patient outcome underlines the importance of systematic hemostatic monitoring over time in TBI.

Monitoring cerebral oxygenation in traumatic brain injury

Ischemia is a common problem after traumatic brain injury (TBI) that eludes detection with standard monitoring. In this review we will discuss four available techniques (SjVO2, PET, NIRS and PbrO2) to monitor cerebral oxygenation. We present technical data including strengths and weaknesses of these systems, information from clinical studies and formulate a vision for the future.

Refining Resuscitation Strategies Using Tissue Oxygen and Perfusion Monitoring in Critical Organ Beds

BACKGROUND Muscle tissue oxygen monitoring (PmO2) holds promise as a continuous guide to resuscitation after hemorrhagic shock, but the relationship of muscle tissue oxygen to perfusion has not been described previously. On the other hand, brain tissue oxygen PbrO2 and perfusion as measured by cerebral blood flow (CBF) are already used clinically, especially as guides to vasopressor use in cerebral perfusion targeted therapy in patients with traumatic brain injury. This laboratory study was undertaken to describe the relative contributions of muscle perfusion and arterial oxygen tension (PaO2) to muscle tissue oxygen (PmO2) levels. Second, we wanted to compare the relationship between muscle oxygen and muscle blood flow (MBF) with simultaneously measured brain tissue oxygen and perfusion during the administration of a vasopressor and during experimental hemorrhagic shock. We hypothesized that muscle perfusion would be an important contributor to PmO2, thus underscoring the need for optimal fluid resuscitation after shock. We further hypothesized that PmO2 would decrease even as PbrO2 increased when vasopressor therapy was used. METHODS Eight pigs were anesthetized, intubated, underwent splenectomies, and were instrumented to monitor PmO2, MBF, PbrO2, and CBF. Oxygen challenges were performed by increasing PaO2 from 100 to 500 mm Hg during three different experimental phases: baseline, vasopressor administration, and hemorrhage. Mean PmO2 and MBF were compared at the beginning and end of each experimental phase and correlations between PmO2, MBF, PbrO2, CBF, and traditional endpoints of resuscitation were investigated. RESULTS During oxygen challenges in all phases, PmO2 increased (31.2 +/- 16.6 mm Hg to 56.6 +/- 34.1 mm Hg; p < 0.01), whereas MBF did not change significantly (16.4 +/- 11.3 mL/100 g/min to 15.4 +/- 11.9 mL/100 g/min). On administration of vasopressors, MBF decreased (18 +/- 8.8 mL/100 g/min to 5.3 +/- 3 mL/100 g/min; p = 0.03), but no change in PmO2 was detected. During hemorrhage, both PmO2 and MBF declined (PmO2: 40 +/- 8.8 mm Hg to 7.7 +/- 9.6 mm Hg; p = 0.002; MBF: 9.8 +/- 5.8 mL/100 g/min to 3.3 +/- 2.4 mL/100 g/min; p = 0.046). Both PmO2 and MBF showed strong relationships with measurements of resuscitation, base deficit (PmO2 and MBF: p < 0.01), and mean arterial pressure (PmO2: p < 0.01, MBF: p = 0.02). Like PmO2 and MBF, PbrO2 and CBF decreased uniformly during hemorrhage. However, on vasopressor administration, CBF and PbrO2 increased significantly, whereas MBF decreased. CONCLUSION PmO2 and MBF can be monitored simultaneously and continuously and correlate well with measurements of resuscitation. PmO2 values reflect both local perfusion and arterial oxygen tension. The clinical application of PmO2 as a continuous endpoint of resuscitation and its relationship to muscle perfusion warrants further study in critically injured patients and these investigations may help to refine resuscitation strategies.

In vitro comparison of two generations of Licox and Neurotrend catheters

BACKGROUND Clinical reports on brain tissue oxygen tension differ in suggested threshold values for defining cerebral ischemia using the Licox and Neurotrend/Paratrend system. We evaluated in vitro performance of both first and second generation devices. MATERIALS AND METHODS Response rate and accuracy in solutions with oxygen tensions from 0 to 150 mm Hg were measured. FINDINGS Ninety-five percent Response times were 102 +/- 13 seconds for first generation Licox probes and 135 +/- 24 s for Paratrend (n = 6, each probe), with second generation probes at 134 +/- 4 and 116 +/- 16 s respectively. At pO2 150 mmHg Licox and Paratrend probes were accurate with 2.2% and 2.1% error, respectively and 2.6% and 4.1% for later generation. At pO2 18 mmHg, Paratrend overestimated by 16.5% (absolute error range 2.18 to 4.18 mmHg), 7.4% for Neurotrend, Licox underestimated by 1.8% (absolute error range 0.08 to 0.52 mmHg) with 3.6% for the second generation probe. CONCLUSIONS Differences between the first generation probe types, while statistically significant (p < 0.001), may not be clinically relevant. Overestimation of pO2 by Neurotrend and small underestimation by Licox partially explain differences in published thresholds for cerebral ischemia. The Neurotrend was slightly more accurate and faster than the Paratrend system.

Efficacy and Safety of Switching to Pasireotide in Patients With Acromegaly Controlled With Pegvisomant and First-Generation Somatostatin Analogues (PAPE Study)

Aim To assess the efficacy and safety of pasireotide long-acting release (PAS-LAR) alone or in combination with pegvisomant by switching patients with acromegaly who were well controlled with long-acting somatostatin analogues (LA-SSAs) and pegvisomant to PAS-LAR with or without pegvisomant. Methods Sixty-one patients with acromegaly were enrolled in a prospective open-label study. We included patients with an insulin-like growth factor I (IGF-I) ≤1.2 × upper limit of normal (ULN) during treatment with LA-SSAs and pegvisomant. At baseline, the pegvisomant dose was reduced by 50% up to 12 weeks. When IGF-I remained ≤1.2 × ULN after 12 weeks, patients were switched to PAS-LAR 60 mg monotherapy. When IGF-I was >1.2 × ULN, patients were switched to PAS-LAR 60 mg, and they continued with the 50% reduced pegvisomant dose. Results At baseline, mean IGF-I was 0.97 × ULN, and the median pegvisomant dose was 80 mg/wk. At 12 weeks, mean IGF-I increased to 1.59 × ULN, and IGF-I levels ≤1.2 ULN were observed in 24.6% of participants. At 24 weeks, IGF-I levels were reduced into the reference range in 73.8% of patients. Between baseline and 24 weeks, the pegvisomant dose was reduced by 66.1%. PAS-LAR was well tolerated, but hyperglycemia was the most frequent adverse event. The frequency of diabetes increased from 32.8% at baseline to 68.9% at 24 weeks. Conclusions Switching to PAS-LAR, either as monotherapy or combination with pegvisomant, can control IGF-I levels in most patients. PAS-LAR demonstrated a pegvisomant-sparing effect of 66% compared with the combination with LA-SSAs. Hyperglycemia was the most important safety issue.