Search

Objectives To evaluate the ultrasonographic measurement of optic nerve sheath diameter (ONSD) as a predictor of intracranial hypertension as compared to the invasive measurement of intracranial pressure (ICP). Design Cross-sectional observational study. Setting Intensive Care Unit (ICU) of two tertiary university hospitals in Montevideo, Uruguay. Patients We included 56 adult patients, over 18 years of age, who required sedation, mechanical ventilation, and invasive ICP monitoring as a result of a severe acute neurologic injury (traumatic or non-traumatic) and had a Glascow Coma Score (GCS) equal to or less than 8 on admission to the ICU. Interventions Ultrasonographic measurement of ONSD to detect intracranial hypertension. Measurements and main results In our study, a logistic regression model was performed in which it was observed that the variable ONSD is statistically significant with a p value of 0.00803 ( 20 mmHg are correctly identified). Conclusions In sedated neurocritical patients, with structural Acute Brain Injury, the ONSD measurement correlates with the invasive measurement of ICP. It was observed that with ONSD values less than 5.7 mm, the probability of being in the presence of ICP above 20 mmHg is very low, while for ONSD values greater than 5.7 mm, said probability clearly increases.

Resumen Objetivo Evaluar el impacto de la infusion de lactato de sodio 0,5 M sobre variables del medio interno y sobre la presion intracraneana en pacientes criticos. Diseno Estudio prospectivo experimental de cohorte unica. Ambito Unidad de cuidados intensivos de un hospital universitario. Pacientes Pacientes con shock y neurocriticos con hipertension intracraneana. Intervenciones Se infundio una carga de 500 cc de infusion de lactato de sodio 0,5 M en 15 min y se midio el nivel plasmatico de sodio, potasio, magnesio, calcio, cloro, lactato, bicarbonato, PaCO2 arterial, pH, fosfato y albumina en 3 tiempos: T0 preinfusion; T1 a los 30 min y T2 a los 60 min postinfusion. Se midieron la presion arterial media y presion intracraneana en T0 y T2. Resultados Recibieron el fluido N = 41: n = 19 como osmoagente y 22 como expansor. Se constato alcalosis metabolica: T0 vs. T1 (p = 0,007); T1 vs. T2 (p = 0,003). La natremia aumento en los 3 tiempos (T0 vs. T1; p Conclusiones La infusion de lactato de sodio 0,5 M genera alcalosis metabolica, hipernatremia, disminucion de la cloremia y un cambio bifasico del lactato, y muestra eficacia en el descenso de la presion intracraneana en pacientes con dano encefalico agudo.

Objective To evaluate the impact of the infusion of sodium lactate 500 ml upon different biochemical variables and intracranial pressure in patients admitted to the intensive care unit. Design A prospective experimental single cohort study was carried out. Scope Polyvalent intensive care unit of a university hospital. Patients Critical patients with shock and intracranial hypertension. Procedure A 500 ml sodium lactate bolus was infused in 15 min. Plasma levels of sodium, potassium, magnesium, calcium, chloride, lactate, bicarbonate, PaCO2, pH, phosphate and albumin were recorded at 3 timepoints: T0 pre-infusion; T1 at 30 min, and T2 at 60 min post-infusion. Mean arterial pressure and intracranial pressure were measured at T0 and T2. Results Forty-one patients received sodium lactate: 19 as an osmotically active agent and 22 as a volume expander. Metabolic alkalosis was observed: T0 vs. T1 (p = 0.007); T1 vs. T2 (p = 0.003). Sodium increased at the 3 timepoints (T0 vs. T1, p Conclusions The infusion of sodium lactate is associated to metabolic alkalosis, hypernatremia, reduced chloremia, and a biphasic change in plasma lactate levels. Moreover, a decrease in intracranial pressure was observed in patients with acute brain injury.

Objectives: To determine the predictive value of the measurement of the diameter of the optic nerve sheath (ONSD) with ocular ultrasonography compared to invasive intracranial pressure (ICP) measurement for the detection of intracranial hypertension (ICH). Design: Prospective, observational study. Setting: Intensive Care Unit (ICU) of two tertiary university hospitals in Montevideo, Uruguay. Patients: We studied 56 adult patients of both sexes, over 18 years of age, who required sedation, mechanical ventilation, and invasive ICP monitoring (patients with severe, traumatic and non-traumatic AEI) with a Glascow Coma Score (GCS) equal to or less than 8 on admission to the ICU. Interventions: This was a study that utilized non-invasive (minimal risk) ultrasonography in patients admitted to the ICU. Measurements and main results: In our study, a logistic regression model was performed in which it was observed that the variable ONSD is statistically significant with a p value of 0.00803 ( 20 mmHg are correctly identified). Conclusions: In sedated neurocritical patients, with structural Acute Brain Injury, the ONSD measurement strongly correlates with the ICP values measured invasively.

Cerebral critical closing pressure (CrCP) comprises intracranial pressure (ICP) and arteriolar wall tension (WT). It is the arterial blood pressure (ABP) at which small vessels close and circulation stops. We hypothesized that the increase in WT secondary to a systemic hypertensive challenge would lead to an increase in CrCP and that the "effective" cerebral perfusion pressure (CPPeff; calculated as ABP - CrCP) would give more complete information than the "conventional" cerebral perfusion pressure (CPP; calculated as ABP - ICP).This study aimed to compare CrCP, CPP, and CPPeff changes during a hypertensive challenge in patients with a severe traumatic brain injury.Data on ABP, ICP, and cerebral blood flow velocity, measured by transcranial Doppler ultrasound, were acquired simultaneously for 30 min both basally and during a hypertensive challenge. An impedance-based CrCP model was used.The following values are expressed as median (interquartile range). There were 11 patients, aged 29 (14) years. CPP increased from 73 (17) to 102 (26) mmHg (P ≤ 0.001). ICP did not change. CrCP changed from 23 (11) to 27 (10) mmHg (P ≤ 0.001). WT increased from 7 (5) to 11 (7) mmHg (P ˂ 0.005). CPPeff changed less than CPP.The CPP change was greater than the CPPeff change, mainly because CrCP increased simultaneously with the WT increase as a result of the autoregulatory response. CPPeff provides information about the real driving force generating blood movement.

A 26-year-old woman presented a superior sagittal and transverse sinus thrombosis with venous infarction. Anticoagulation was started. Six months later headache and visual impairment developed, and intracranial hypertension was diagnosed-secondary pseudotumor cerebri. It was managed with a lumbo-peritoneal shunt (LPS) resulting in a positive initial evolution with initial symptoms resolution, but headache and visual impairment eventually reappeared. Magnetic Resonance Imaging revealed a Pseudo-Chiari malformation, leading to lumbo-peritoneal shunt removal (Friedman et al. Neurology 81:1159-1165, 2013; Moncho et al. Rev Neurol 56(12):623-634, 2013). As symptoms reappeared, a short period of continuous transcranial Doppler neuromonitoring, including a change of head of bed elevation, was performed. A sudden decrease in cerebral blood flow velocity with a dramatic increase in pulsatility index developed when head of bed was moved from 45° to horizontal position. Transcranial Doppler changes were compatible with a plateau wave of intracranial hypertension. A ventricle-peritoneal shunt was inserted, which resulted in symptomatology, imaging, and digital campimetry improvement.

Introduction: Cerebral critical closing pressure (CrCP) comprises intracranial pressure (ICP) and arteriolar wall tension (WT). It is the arterial blood pressure (ABP) at which small vessels close and circulation stops. We hypothesized that the increase in WT secondary to a systemic hypertensive challenge would lead to an increase in CrCP and that the “effective” cerebral perfusion pressure (CPPeff; calculated as ABP − CrCP) would give more complete information than the “conventional” cerebral perfusion pressure (CPP; calculated as ABP − ICP).

Objectives To evaluate the correlation between ultrasonographic and infrared pupillary assessments in critically ill patients, including neurocritically ill patients. Design Prospective, observational study. Setting Tertiary teaching hospital intensive care unit (ICU) in Montevideo, Uruguay. Patients Twenty-six adults patients with age 18 or older admitted to the intensive care unit with and without neurologic pathology. A total of 212 pupillary measures were made between ultrasonographic pupillary assessment (UPA) and infrared pupillary assessment (IPA). Interventions This was a study that utilized non-invasive (minimal risk) ultrasonographic and infrared pupillary assessment in patients admitted to the ICU. Time between UPA and IPA in a single patient was consistently less than 3 min. Measurements and main results There was a strong positive association between UPA and IPA (right eye [OD]: r = de 0.926, p-value r = 0.965, p-value r = 0.935, p-value r = de 0.965, p-value Conclusions Ultrasonographic pupillary assessment is strongly correlated with infrared pupillary assessment in critically ill patients, including neurocritically ill patients. Ultrasonographic pupillary assessment is a quick, feasible, non-invasive method that allows accurate pupillary assessment, particularly neurologic function, in patients in whom a more precise measurement of the pupil is required or eye opening is not possible (e.g., periorbital edema due to traumatic brain injury).

To evaluate cerebrospinal fluid (CSF) and peripheral blood (PB) Treg, TH17 cells, TH1, TH2 and related cytokines in the acute phase of aSAH we assessed TH17, TH1, TH2, T regulatory cells and neutrophils in 39 aneurysmal subarachnoid hemorrhage (aSAH) patients and 56 controls. PB TH17 cells and TH17/Treg ratio were higher in CSF and PB of aSAH patients. Serum and CSF IL-17A levels were increased in aSAH. Serum IL-17A levels were associated with vasospasm and ICU mortality. Study results support the role of TH17/IL17 axis in aSAH pathogenesis, turning it into a potential clinical biomarker and a novel target for research.

Objective To evaluate the value of CSF lactate (LCSF) for the diagnosis of ventriculostomy related infections (VRI), and compare it with other CSF markers. Methods Prospective study of neurocritical patients admitted to Maciel Hospital and Clinicas Hospital ICUs in which an external ventricular drain (EVD) was inserted. In patients with clinical suspicion of VRI, a CSF sample was obtained through the EVD for CSF culture and markers analysis (glucose, protein, lactate and leukocytes). We defined proven VRI according to preset criteria as: fever, plus CSF alterations (glucose 500/μl), plus positive CSF culture. CSF markers were plotted in a receiver operating curve (ROC) to evaluate their diagnostic accuracy. Results 36 CSF samples were obtained: 14 corresponded to proven VRI and 22 to excluded VRI. Median LCSF was 9.90 mmol/L (IQR: 4.7–12) for proven VRI versus 2.95 mmol/L (IQR: 2.4–3.6) for excluded VRI (p Conclusions For the studied population, LCSF represents a good marker for VRI. It could be used as a quick and specific test to identify the need for antimicrobial therapy in patients with clinical suspicion of VRI.

Cerebral critical closing pressure (CrCP) is the level of arterial blood pressure (ABP) at which small brain vessels close and blood flow stops. This value is always greater than intracranial pressure (ICP). The difference between CrCP and ICP is explained by the tone of the small cerebral vessels (wall tension). CrCP value is used in several dynamic cerebral autoregulation models. However, the different methods for calculation of CrCP show frequent negative values. These findings are viewed as a methodological limitation. We intended to evaluate CrCP in patients with severe traumatic brain injury (TBI) with a new multiparameter impedance-based model and compare it with results found earlier using a transcranial Doppler (TCD)-ABP pulse waveform-based method.Twelve severe TBI patients hospitalized during September 2005-May 2007. Ten men, mean age 32 years (16-61). Four had decompressive craniectomies (DC); three presented anisocoria. Patients were monitored with TCD cerebral blood flow velocity (FV), invasive ABP, and ICP. Data were acquired at 50 Hz with an in-house developed data acquisition system. We compared the earlier studied "first harmonic" method (M1) results with results from a new recently developed (M2) "multiparameter method."M1: In seven patients CrCP values were negative, reaching -150 mmHg. M2: All positive values; only one lower than ICP (ICP 60 mmHg/ CrCP 57 mmHg). There was a significant difference between M1 and M2 values (M1 M2) and between ICP and M2 (M2 ICP).M2 results in positive values of CrCP, higher than ICP, and are physiologically interpretable.

Intracranial hypertension (ICH) is the most important modifiable factor with predictive negative value in brain injury patients. Osmotherapy is the most important first level specific measure in the treatment of ICH. Mannitol 20%, and 3, 7.5, 10, and 23% hypertonic sodium chloride are the most commonly used osmotic agents in the neurocritical care setting. Currently, controversy about the best osmotic agent remains elusive. Therefore, over the past few years, half-molar sodium lactate has been introduced as a new osmotic agent to be administered in the critically ill. Lactate is able to prevent hyperchloremia, as well as its adverse effects such as hyperchloremic acidosis, systemic inflammation, and acute kidney injury. Furthermore, lactate may also be used by glia as energy substrate in brain injury patients. Half-molar sodium lactate would also have a more potent and long-lasting effect decreasing intracellular osmolarity and by inhibiting neuronal volume control mechanisms. Pioneering researches in patients with traumatic brain injury have shown a more significant effect than mannitol on the control of ICH. In addition, in this group of patients this solution appears to be beneficial in preventing episodes of ICH. However, future research is necessary to corroborate or not these promising results.

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of "cerebral salt wasting", which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of “cerebral salt wasting”, which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

To describe a direct intra-abdominal pressure (IAP) measurement technique using a solid microsensor comparing its values with the ones simultaneously obtained by means of Kron's technique. Comparative study between two different methods to measure intra-abdominal pressure in a multidisciplinary intensive care unit of a university hospital.In 11 critical patients considered irreversibly ill, IAP was simultaneously measured via Kron's technique (IAPK) and by direct measure (IAPC) through an abdominal tap with a Codman microsensor, inserted through it. Several measurements were obtained at different PEEP levels (0, 10 and 20 cm of H20) and bed inclination (0 degrees , 40 degrees and 60 degrees ).92 simultaneous measurements of IAPK and IAPC were made. The difference between both measurements (mean +/- SD) were: 0.286 +/- 0.938 mmHg. The correlation coefficient was r = 0.98. Bland-Altman plot showed a narrow distribution: 95% of the differences were between 1.87 mmHg of each averaged value. No complications with IAPC measurements were found.Direct IAP measurement with a Codman microsensor allows continuous monitoring without urinary tract manipulation, is simple to use and to calibrate, minimally invasive and appropriate for patients at risk to develop abdominal compartmental syndrome. Due to its cost it should be reserved for selected critical patients where standard techniques are contraindicated or can be inaccurate.

Intracranial hypertension (ICH) is the most important modifiable factor with predictive negative value in brain injury patients. Osmotherapy is the most important first level specific measure in the treatment of ICH. Mannitol 20%, and 3, 7.5, 10, and 23% hypertonic sodium chloride are the most commonly used osmotic agents in the neurocritical care setting. Currently, controversy about the best osmotic agent remains elusive. Therefore, over the past few years, half-molar sodium lactate has been introduced as a new osmotic agent to be administered in the critically ill. Lactate is able to prevent hyperchloremia, as well as its adverse effects such as hyperchloremic acidosis, systemic inflammation, and acute kidney injury. Furthermore, lactate may also be used by glia as energy substrate in brain injury patients. Half-molar sodium lactate would also have a more potent and long-lasting effect decreasing intracellular osmolarity and by inhibiting neuronal volume control mechanisms. Pioneering researches in patients with traumatic brain injury have shown a more significant effect than mannitol on the control of ICH. In addition, in this group of patients this solution appears to be beneficial in preventing episodes of ICH. However, future research is necessary to corroborate or not these promising results.

Background There is growing evidence supporting the role of inflammation in aneurysmal subarachnoid hemorrhage (aSAH) pathophysiology and it is of great interest to elucidate which immune mechanisms are involved. Methods 12 aSAH patients and 28 healthy controls were enrolled prospectively. We assessed leukocytes subpopulations and their activation status by flow cytometry in cerebrospinal fluid (CSF) and peripheral blood (PB) of SAH patients at the same time and in PB of controls. Results Monocytes and neutrophils were activated in CSF of aSAH patients. The percentage of CD14++CD16+ monocytes were higher in CSF than in PB of aSAH patients, and were also increased in PB of aSAH patients compared with controls. An enhanced expression of CD69 was shown in CSF neutrophils compared with PB in aSAH patients. PB of aSAH patients showed lower percentage of total lymphocytes compared with controls PB. Additionally, lymphocytes were activated in CSF and PB of aSAH patients. CD4+ and CD8+ T cells had a decreased expression on CD3 and higher levels of CD69 in CSF compared with PB in aSAH patients. Moreover, PB CD4+ and CD8+ T cells of aSAH patients were activated compared with controls. Additionally, CD28 expression was decreased on CSF T lymphocytes. Conclusions Our data suggest an important recruitment of leukocytes to the site of injury in aSAH as well as an increased activation at this level. Overall, these results indicate that aSAH probably stimulates both the innate and adaptive immune responses.

La dexmedetomidina, un agonista adrenérgico selectivo α2, constituye un intento de mejorar la sedoanalgesia de los pacientes críticos, por sus efectos distintivos en comparación a los planes tradicionales como son: sedación consciente, simpaticolisis y ausencia de depresión respiratoria. Objetivo. Estudiar el efecto de la dexmedetomidina, un nuevo agonista α28, sobre la hemodinámica intracraneal y sobre los parámetros hemometabólicos cerebrales en un grupo de pacientes con trauma craneoencefálico grave. Material y métodos. Estudio prospectivo de los pacientes con lesión encefálica traumática grave (Glasgow Coma Scale ≤ 8) ingresados en un Centro de Tratamiento Intensivo (CTI) que recibieron monitorización de la presión intracraneal (PIC) y monitorización de saturación de O2 del bulbo yugular (SjO2). Se realizó una perfusión intravenosa de la droga durante 3 horas, en dosis progresivas (0.2, 0.4 y 0.7 ug/kg/h), previa suspensión de otros sedantes y analgésicos. Resultados. Se estudiaron 12 pacientes sin hipertensión intracraneal. No se encontraron diferencias significativas entre los valores de PIC y presión arterial media (PAM) tras la infusión de la droga en relación con los valores basales. La presión de perfusión cerebral (PPC) mostró una tendencia a disminuir durante el estudio (efecto marginal, p=0.058). Se encontró un descenso significativo de la frecuencia cardíaca (FC) (p

a large number of editorials, reviews, and new studies have addressed the issue of whether the monitoring of intracranial pressure (ICP) is relevant in the management of severe head injury and whether the costs are justified to achieve a better outcome. The article “Measurement of intracranial pressure and short-term outcome of patients with traumatic brain injury: a propensity-matched analysis” by Biselli-Ferreira et al.

The management of severe head injuries in general and that of high intracranial pressure (ICP) in particular are among the most challenging tasks in neurocritical care. One of the difficulties still faced by clinicians is that of reducing variability among centers when implementing management protocols. The purpose of this paper is to propose a standardized protocol for the management of high ICP after severe head injury, consistent with recently published clinical practice guidelines and other clinical evidence such as that provided by the systematic reviews of the Cochrane Collaboration. Despite significant advances in neuromonitoring, deeper insight into the physiopathology of severe brain trauma and the many therapeutic options available, standardized protocols are still lacking. Recently published guidelines provide sketchy recommendations without details on how and when to apply different therapies. Consequently, great variability exists in daily clinical practice even though different centers apply the same evidence-based recommendations. In this paper we suggest a structured protocol in which each step is justified and integrated into an overall strategy for the management of severe head injuries. The most recent data from both the preliminary and definitive results of randomized clinical trials as well as from other sources are discussed. The main goal of this article is to provide neurotraumatology intensive care units with a unified protocol that can be easily modified as new evidence becomes available. This will reduce variation among centers when applying the same therapeutic measures. This goal will facilitate comparisons in outcomes among different centers and will also enable the implementation of more consistent clinical practice in centers involved in multicenter clinical trials.

This article describes a device for the reduction of intra-abdominal pressure. The device (ABDOPRE) includes a unique external servo-control mechanism, based on urinary bladder pressure measurement. The results of ABDOPRE use in the first four intra-abdominal hypertension patients are reported; the device resulted in a reduction of intra-abdominal pressure between 16% and 35% in 3 cases and in a paradoxical increase of the intra-abdominal pressure in an obese woman, likely due to inappropriate chamber size for the patient's anatomy. These results are promising and ABDOPRE may be useful in clinical practice.

In the neurocritical care setting, hyponatremia is the commonest electrolyte disorder, which is associated with significant morbimortality. Cerebral salt wasting and syndrome of inappropriate antidiuretic hormone have been classically described as the 2 most frequent entities responsible of hyponatremia in neurocritical care patients. Nevertheless, to distinguish between both syndromes is usually difficult and useless as volume status is difficult to be determined, underlying pathophysiological mechanisms are still not fully understood, fluid restriction is usually contraindicated in these patients, and the first option in the therapeutic strategy is always the same: 3% hypertonic saline solution. Therefore, we definitively agree with the current concept of "cerebral salt wasting", which means that whatever is the etiology of hyponatremia, initially in neurocritical care patients the treatment will be the same: hypertonic saline solution.

Traumatic brain injury initiates several metabolic processes that can increase the primary injury. It is well established that in severe head injuries, posttraumatic secondary insults, such as brain hypoxia, hypotension or anemia, exacerbate neuronal injury and lead to a poorer outcome. Experimental and clinical evidence suggests that moderate hypothermia (32-34 degrees C), may limit some of these deleterious secondary metabolic responses. Recent laboratory studies and prospective controlled clinical trials of induced moderate hypothermia for relatively short periods (24-48 h) in patients with severe head injury, have demonstrated good intracranial pressure control and better outcome when compared with patients maintained in normothermia and given conventional treatment. Despite its proven clinical role in neuroprotection, hypothermia research has been inconstantly followed for various reasons. In this paper we review the mechanisms of neuroprotection in hypothermia, the different preclinical and clinical studies that favor its use as a neuroprotector in severe head injury or in patients in whom high intracranial pressure is refractory to first tier measures. The evidence that favors hypothermia is discussed. We also discuss the negative results of the still unpublished multicentre trial on prophylactic moderate hypothermia developed in the USA. The main problem with moderate hypothermia is the lack of a systematic methodology to induce and maintain it. Also, optimal duration of its use and the methodology and timing for rewarming have not been determined. Consequently, the results of different trials are difficult to analyze and compare. However, most evidence suggests that hypothermia provides remarkable protection against the adverse effects of neuronal damage that is exacerbated by secondary injury. Further prospective controlled trials with clearly defined methodology are needed before this method is implemented in daily clinical practice. The most important task for the years to come may be to focus on refining this procedure, defining the optimal time of cooling and rewarming and to optimize the methods of rapidly inducing and maintaining low temperature. It is also essential to define the most appropriate method and velocity of the rewarming phase, in which many successfully controlled patients deteriorate and die.

Osmotic agents are still the most common treatment for controlling intracranial hypertension (ICH). Mannitol, glycerol, sorbitol, and hypertonic serum saline are the agents currently available. This work was designed to compare mannitol and glycerol in a similar population of brain injured patients, randomly divided into two groups of eight. The following mean day parameters were obtained: number of infusions, hydric balance, mean arterial pressure (MAP), and intracranial pressure (ICP). Cerebral perfusion pressure (CPP) was calculated. Brain computed tomographies (CT) were obtained on arrival, at follow-up whenever justified and at discharge. For comparison of both groups a modified therapeutic intensity level (mTIL) was used. Both agents induced a statistically equally effective decrease on ICP and increase on CPP evaluated at one and two hours post infusion but the mean day mTIL showed a statistically significant difference in favour of glycerol. The possible explanations of this difference are discussed. According to our results mannitol would be most indicated as a bolus to control sudden rises in ICP whereas glycerol would be most indicated as a basal treatment.

✓ The effect of indomethacin, a cyclooxygenase inhibitor, was studied in the treatment of 10 patients with head injury and one patient with spontaneous subarachnoid hemorrhage, each of whom presented with high intracranial pressure (ICP) (34.4 ± 13.1 mm Hg) and cerebral perfusion pressure (CPP) impairment (67.0 ± 15.4 mm Hg), which did not improve with standard therapy using mannitol, hyperventilation, and barbiturates. The patients had Glasgow Coma Scale scores of 8 or less. Recordings were made of the patients' ICP and mean arterial blood pressure from the nurse's end-hour recording at the bedside, as well as of their CPP, rectal temperature, and standard therapy regimens. The authors assessed the effects of an indomethacin bolus (50 mg in 20 minutes) on ICP and CPP; an indomethacin infusion (21.5 ± 11 mg/hour over 30 ± 9 hours) on ICP, CPP, rectal temperature, and standard therapy regimens (matching the values before and during infusion in a similar time interval); and discontinuation of indomethacin treatment on ICP, CPP, and rectal temperature. The indomethacin bolus was very effective in lowering ICP (p < 0.0005) and improving CPP (p < 0.006). The indomethacin infusion decreased ICP (p < 0.02), but did not improve CPP and rectal temperature. The effects of standard therapy regimens before and during indomethacin infusion showed no significant changes, except in three patients in whom mannitol reestablished its action on ICP and CPP. Sudden discontinuation of indomethacin treatment was followed by significant ICP rebound. The authors suggest that indomethacin may be considered one of the frontline agents for raised ICP and CPP impairment.

BACKGROUND Intracranial hypertension is the final pathway of many neurocritical entities, such as spontaneous intracerebral hemorrhage (sICH) and severe traumatic brain injury (sTBI). OBJECTIVE This study aimed to (1) determine alterations in intracranial pressure (ICP) and cerebral hemodynamics after an indomethacin (INDO) infusion test and the related association with survival in patients with refractory intracranial hypertension (RICH) secondary to sICH or sTBI and (2) assess the safety profile after INDO. METHODS INDO was administered in a loading dose (0.8 mg/kg/15 min), followed by a 2-hour continuous infusion (0.5 mg/kg/h) in RICH patients with ICP greater than 20 mm Hg who did not respond to first-line therapies. Changes in ICP, cerebral perfusion pressure (CPP), and cerebrovascular variables (assessed by transcranial Doppler and jugular bulb saturation) were observed. Clinical outcome was assessed at 1 and 6 months according to the Glasgow Outcome Scale and correlated with INDO infusion test response. Analysis of INDO safety profile was conducted. RESULTS Thirteen sICH and 10 sTBI patients were studied. The median GCS score at admission was 6. Within 30 minutes of INDO infusion, ICP decreased (42.0 ± 13.5 vs 27.70 ± 12.7 mm Hg; Δ%: -48.4%; P < .001), and both CPP (57.7 ± 4.8 vs 71.9 ± 7.0 mm Hg; Δ%: +26.0%; P < .001) and middle cerebral artery velocity (35.2 ± 5.6 vs 42.0 ± 5.1 cm·s(-1); Δ%: +26.1%; P < .001) increased. The CPP response to a 2-hour INDO infusion test was correlated (R2 = 0.72, P < .001) with survival. No adverse events were observed after INDO. CONCLUSION Our findings support the effectiveness and feasibility of an INDO test in decreasing ICP and improving cerebral hemodynamics in surviving RICH patients. Future studies to evaluate different doses, lengths of infusion, and longer term effects are needed.

Cerebral critical closing pressure (CrCP) is the arterial pressure (AP) below which small arterial cerebral vessels collapse. Our objective was to estimate cerebral CrCP in 12 severe TBI patients, relating transcranial Doppler flow velocity (FV) and AP data.FV, intracranial pressure (ICP) and invasive AP were prospectively acquired at 50 Hz. CrCP was estimated using three methods (M): M(1): amplitude ratio of FV/AP first harmonics; M(2): AP axis intersection of the regression line between systolic and diastolic values of FV and AP; M(3): AP axis intersection of the regression line between decreasing AP and FV simultaneous values.There were 12 patients. Frequent negative CrCP values were found. Average M(1):-12 mmHg; M(2):-33 mmHg; M(3):-43 mmHg. Correlation between the three methods was significant (P0.01). M(1) showed the lowest range and more positive values. The better limits of agreement (Bland and Altman test) were between M(2) and M(3).The frequently found negative values do not allow us for the moment, to use any of these three methods for clinical guidance.

Objective: Cerebral critical closing pressure (CrCP) is the arterial pressure (AP) below which small arterial cerebral vessels collapse. Our objective was to estimate cerebral CrCP in 12 severe TBI patients, relating transcranial Doppler flow velocity (FV) and AP data. Methods: FV, intracranial pressure (ICP) and invasive AP were prospectively acquired at 50 Hz. CrCP was estimated using three methods (M): M1: amplitude ratio of FV/AP first harmonics; M2: AP axis intersection of the regression line between systolic and diastolic values of FV and AP; M3: AP axis intersection of the regression line between decreasing AP and FV simultaneous values.

Many neurosurgery patients may have unrecognized diabetes or may develop stress-related hyperglycemia in the perioperative period. Diabetes patients have a higher perioperative risk of complications and have longer hospital stays than individuals without diabetes. Maintenance of euglycemia using intensive insulin therapy (IIT) continues to be investigated as a therapeutic tool to decrease morbidity and mortality associated with derangements in glucose metabolism due to surgery. Suboptimal perioperative glucose control may contribute to increased morbidity, mortality, and aggravate concomitant illnesses. The challenge is to minimize the effects of metabolic derangements on surgical outcomes, reduce blood glucose excursions, and prevent hypoglycemia. Differences in cerebral versus systemic glucose metabolism, time course of cerebral response to injury, and heterogeneity of pathophysiology in the neurosurgical patient populations are important to consider in evaluating the risks and benefits of IIT. While extremes of glucose levels are to be avoided, there are little data to support an optimal blood glucose level or recommend a specific use of IIT for euglycemia maintenance in the perioperative management of neurosurgical patients. Individualized treatment should be based on the local level of blood glucose control, outpatient treatment regimen, presence of complications, nature of the surgical procedure, and type of anesthesia administered.

To confirm the pharmacodynamics and evaluate the efficacy of high-dose selenium (Se) administered by continuous infusion, following an initial loading bolus of selenite, on clinical outcome in critically ill patients with systemic inflammatory response syndrome (SIRS). Prospective, placebo-controlled, randomized, single-blinded phase II study in a multidisciplinary university hospital intensive care unit (ICU). Two groups of patients with SIRS, age >18 years, and Acute Physiology and Chronic Health Evaluation (APACHE) II ≥15 (n = 35) were randomized to receive either placebo or intravenous selenite as a bolus-loading dose of 2,000 μg Se followed by continuous infusion of 1,600 μg Se per day for 10 days. Blood samples were analyzed before randomization (day 0) then at days 3, 7, and 10. Clinical outcome was assessed by Sequential Organ Failure Assessment (SOFA) score. Hospital-acquired pneumonia including ventilator-associated pneumonia (VAP), adverse events, and other safety parameters were monitored as secondary endpoints. SOFA score decreased significantly in the selenite group at day 10 (1.3 ± 1.2 versus 4.6 ± 2.0, p = 0.0001). Early VAP rate was lower in the selenite group (6.7% versus 37.5%, p = 0.04), and hospital-acquired pneumonia was lower after ICU discharge (p = 0.03). Glutathione peroxidase-3 (GPx-3) activity increased in both groups, reaching a maximum at day 7 (0.62 ± 0.24 versus 0.28 ± 0.14 U/mL, p = 0.001) in the selenite group. No adverse events attributable to selenite were observed. Daily infusion of 1,600 μg Se (as selenite), following an initial bolus of 2,000 μg, is novel and without short-term adverse events. High-dose parenteral selenite significantly increases Se status, improves illness severity, and lowers incidence of hospital-acquired pneumonia including early VAP for SIRS patients in ICU.

Cerebral circulation is profoundly affected by changes in PaCO2. CO2 manipulation plays a basic role in the management of intracranial hypertension; CO2 reactivity (CO2R) defines the changes in CBF in response to changes in PaCO2. Transcranial Doppler has allowed exploring its effects "on line".We conducted a prospective clinical trial, with the objective of studying CO2R in severe head injury patients. Sixteen severe traumatic brain injury patients, mechanically ventilated, were included. Monitoring of MAP, ICP, CPP, SjO2, ETCO2, and cerebral blood flow velocity (CBFV) was performed. Taking into account basal cerebral hemodynamic pattern, minute ventilation was modified to attain a negative ("A") or positive ("B") deltaPCO2. CO2R was calculated as: CO2R = % deltaCBFV/deltaETCO2 in mmHg (normal value 3.7 +/- 1%/mmHg). CO2R was compared with deltaICP/ deltaPCO2 in each patient.Three patients were excluded because the change in ETCO2 was too low (deltaETCO23 mmHg). The median value of CO2R in the total group of 13 patients was 3.38. In "A" the values tended to be lower than in "B". There were four low CO2R values in "A" and none in "B". There was no significant correlation between CO2R and deltaICP/deltaPCO2.The different "A" and "B" behavior might be due to dissimilar mechanisms involved in the basis of vasodilatation and vasoconstriction. Changes in ventilation must be performed with caution, avoiding sudden increases in CO2 that may increase ICP. The absence of correlation between CO2R and deltaICP/deltaPCO2 is explained, at least partially, by different cranio-cerebral compliance in each patient. Therefore, induced blood volume changes are not directly transmitted to ICP, but their effects depend on the shape of the pressure-volume curve and the position on the curve in which each situation is working.

Objective Systemic inflammatory response syndrome is characterized by increased urinary excretion of selenium and low serum concentration. Repletion by parenteral selenite is the most efficacious form of supplementation. However, the optimum safe dose and mode of administration remain controversial. We aimed to determine pharmacokinetic and pharmacodynamic profiles of selenite and estimate a safe dose to optimize selenium status. Methods A prospective, randomized, pilot study in 20 patients with systemic inflammatory response syndrome compared a high-dose (HD) group that received a loading dose of selenium as selenite 15.18 μmol over 2 h and thereafter 10.12 μmol/d as a continuous intravenous infusion (CIV) for 10 d with a very–high-dose (VHD) group that received a loading dose of 25.30 μmol over 2 h and thereafter 20.24 μmol as a CIV for 10 d. Clinical outcome was evaluated by length of stay in the intensive care unit, incidence of ventilator-associated pneumonia, and Sequential Organ Failure Assessment score. Results Patients in group HD (n = 10, age 54 ± 23 y) had an Acute Physiology and Chronic Health Evaluation II score of 23 ± 5 and a Sequential Organ Function Assessment score of 10 ± 2. Those in group VHD (n = 10, age 41 ± 19 y) had scores of 21 ± 7 and 8 ± 3, respectively. Pharmacokinetic concentration/time curves for serum selenium overlapped but were independent of dose, whereas the pharmacodynamics were different, showing maximum glutathione peroxidase activity only with VHD. Glutathione peroxidase decreased after day 7 independently of the selenium dose. Clinical outcomes were similar in both groups. Conclusion A bolus loading dose of selenite providing 2000 μg of selenium (25.30 μmol) followed by a CIV of 1600 μg/d (20.24 μmol/d) for 10 d is most effective at returning serum selenium to physiologic levels and safely maximizing glutathione peroxidase activity.

To evaluate the feasibility, safety and effectiveness of a new method of intravascular temperature management for inducing moderate hypothermia (MHT).Prospective, international-multicenter clinical trial conducted in four university hospitals.In a 2-year period 24 patients with severe head injury and refractory high ICP were treated with MHT (32.5 degrees C) by intravascular methods.Seventeen were males and seven females, with a median age of 25 years (range 15-60). The median Glasgow Coma Scale upon admission was 7 (range 3-13) and the median Injury Severity Score was 22 (range 13-43). A total of 75% of patients presented a diffuse lesion in the pre-enrollment computed tomography. Median time from injury until reaching refractory high ICP was 71.5 h after injury (minimum 14 h, maximum 251 h). Twelve patients (50%) reached this situation within the first 72 h after injury. MHT was attained in a median time of 3 h. Pre-enrollment median ICP was 23.8 mmHg and was reduced to 16.8 mmHg upon reaching target temperature. At 6 months after injury, nine patients had died (37.5%), six were severely disabled (25%), two moderately disabled (8.3%) and seven had a good recovery (29.2%). Of the nine patients who died, in four the cause was rebound ICP during rewarming, one death was attributed to accidental potassium overload, two to septic shock, one to cardiac arrest of unknown origin and the ninth to a pulmonary embolism.Intravascular methods to induce MHT combined with precooling with cold saline at 4 degrees C appear to be feasible and effective in reducing ICP in patients with high ICP refractory to first-line therapeutic measures.

To compare dynamic and static responses of cerebral blood flow to sudden or slow changes in arterial pressure in severe traumatic brain injury (TBI) patients. Prospective study. We studied 12 severe TBI patients, age 16–63 years, and median GCS 6. We determined the dynamic cerebral autoregulation: response of cerebral blood flow velocity to a step blood pressure drop, and the static cerebral autoregulation: change in cerebral blood flow velocity after a slow hypertensive challenge. During the dynamic response, the median drop in arterial pressure was 21 mm Hg. Dynamic response was graded between 9 (best) and 0 (worst). The median value was 5; four patients showed high values, (8–9), five patients showed intermediate values (4–6). In three patients (value = 0), the CBFV drop was greater than the cerebral perfusion pressure drop, and maintained through 60 s. The static cerebral autoregulation was preserved in 6/11 patients. The comparison between the two showed four different combinations. The five patients with impaired static cerebral autoregulation showed unfavorable outcome. A sharp dynamic vasodilator response could not be sustained, and a slow or absent reaction to a sudden hypotensive challenge could show an acceptable cerebral autoregulation in the steady state. We found that patients with impaired static cerebral autoregulation had a poor outcome, whereas those with preserved static cerebral autoregulation experience favorable outcomes.

Background Cerebral circulation is profoundly affected by changes in PaCO2 .C O2 manipulation plays a basic role in the management of intracranial hypertension; CO2 reactivity (CO2R) defines the changes in CBF in response to changes in PaCO2. Transcranial Doppler has allowed exploring its effects “on line”. Materials and methods We conducted a prospective clinical trial, with the objective of studying CO2R in severe head injury patients. Sixteen severe traumatic brain injury patients, mechanically ventilated, were included. Monitoring of MAP, ICP, CPP, SjO2 ,E TCO2, and cerebral blood flow velocity (CBFV) was performed. Taking into account basal cerebral hemodynamic pattern, minute ventilation was modified to attain a negative (“A” )o r positive (“B”) ΔPCO2 .C O2 Rw as calculated as: CO2R=%ΔCBFV/ΔETCO2 in mmHg (normal value 3.7±1%/mmHg). CO2R was compared with ΔICP/ ΔPCO2 in each patient. Findings Three patients were excluded because the change in ETCO2 was too low (ΔETCO2 < 3 mmHg). The median value of CO2R in the total group of 13 patients was 3.38. In “A” the values tended to be lower than in “B”. There were four low CO2 Rv alues in“A” and none in “B”. There was no significant correlation between CO2 Ra ndΔICP/ΔPCO2. Conclusions The different “A” and “B” behavior might be due to dissimilar mechanisms involved in the basis of vasodilatation and vasoconstriction. Changes in ventilation must be performed with caution, avoiding sudden increases in CO2 that may increase ICP. The absence of correlation between CO2R and ΔICP/ΔPCO2 is explained, at least partially, by different cranio-cerebral compliance in each patient. Therefore, induced blood volume changes are not directly transmitted to ICP, but their effects depend on the shape of the pressure-volume curve and the position on the curve in which each situation is working.

Objective. To assess the effect of indomethacin on cerebral autoregulation, systemic and cerebral haemodynamics, in severe head trauma patients. Design. Prospective, controlled clinical trial, with repeated measurements. Settings. A 12-bed adult general intensive care unit in a third level referral university hospital. Patients. 16 severely head injured patients, 14 males, age range 17–60. Interventions. Indomethacin was administrated as a load plus continuous infusion. Indomethacin reactivity was assessed as the estimated cerebral blood flow change elicited by the load. Dynamic and static cerebral autoregulation tests were performed before indomethacin administration, and during its infusion. Measurements and main results. Systemic and cerebral haemodynamic changes were assessed through continuous monitoring of mean arterial pressure, transcranial Doppler cerebral blood flow velocity, intracranial pressure, cerebral perfusion pressure, and jugular venous oxygen saturation. Indomethacin loading dose was immediately followed by a cerebral blood flow median decrease of 36 or 29% (p = ns) evaluated by two different methods, by an ICP decrease and by an AVDO2 increase from 3.52 to 6.15 mL/dL (p = 0.002). Dynamic autoregulation increased from a median of 28 to 57% (p

Dexmedetomidine, an alpha 2 adrenergic agonist, with distinctive characteristics when compared to traditional plans, namely: conscious sedation, sympatholysis and lack of respiratory depression, represents an attempt to improve the sedoanalgesia of critically ill patients. OBJECTIVE. To study dexmedetomidine's effect on intracranial hemodynamic and hemometabolic parameters in severe head injured patients. MATERIAL AND METHODS. Prospective study on the effect of Dexmedetomidine on twelve severe head injured patients (Glasgow Coma Scale scoreor= 8) admitted to an intensive care unit, with intracranial pressure20 mmHg and O(2) saturation monitoring of blood from jugular bulb. The drug was perfused intravenously during 3 hours, in progressive doses (0.2, 0.4 and 0.7 ug/kg/h). All other sedo-analgesia medication had been previously withdrawn. RESULTS. No significant differences were found in intracranial pressure, mean arterial pressure and cerebral hemometabolic parameters after infusion of dexmedetomidine in relation to basal values. Cerebral perfusion pressure showed a trend to decrease during the drug infusion (marginal effect, p =.058). Cardiac frequency decreased significantly after the drug administration. CONCLUSIONS. At the doses utilized, dexmedetomidine was safe, and it was not associated with significant changes in intracranial hemodynamics, nor in cerebral hemometabolic parameters, in a group of severe head jnjured patients.

Cerebral static autoregulation (AR) was evaluated at bedside in 14 severely head injured patients. 16 investigations were performed. Cerebral perfusion pressure (CPP) was increased by infusing vasopressors during one hour, and registered every 2-5 minutes. CBF was simultaneously estimated by: 1) middle cerebral artery mean flow velocity (FV) monitoring with Transcranial Doppler (TDC), and 2) the reciprocal of arteriovenous oxygen content difference, calculated from basal and hypertensive arterial and jugular bulb blood samples. AR assessment: For TCD results, linear regression method was used, studying two pairs of variables: a) %FV-CPP (the regression slope was the main AR value adopted) and b) % cerebrovascular resistance (CVR)-%CPP. For the AVDO2 method, autoregulation was considered preserved if estimated % delta CBF/delta PPE1%/mm Hg. TCD method clearly defined three groups. Group 1 and 2 (8 and 5 investigations) were considered as two grades of preserved AR, and the third one (3 cases) as impaired AR. AVDO2 method: 12 studies were evaluated. 10 showed preserved AR, and 2 impaired AR. There was coincidence of results from both methods in 10 out of 12 studies. (0.83).

Cerebral static autoregulation (AR) was evaluated at bedside in 14 severely head injured patients. 16 investigations were performed. Cerebral perfusion pressure (CPP) was increased by infusing vasopressors during one hour, and registered every 2–5 minutes. CBF was simultaneously estimated by: 1) middle cerebral artery mean flow velocity (FV) monitoring with Transcranial Doppler (TDC), and 2) the reciprocal of arteriovenous oxygen content difference, calculated from basal and hypertensive arterial and jugular bulb blood samples. AR assessment: For TCD results, linear regression method was used, studying two pairs of variables: a) %FV-CPP (the regression slope was the main AR value adopted) and b) % cerebrovascular resistance (CVR)-%CPP. For the AVD02 method, autoregulation was considered preserved if estimated %ΔCBF/ ΔPPE < 1%/mm Hg. TCD method clearly defined three groups. Group 1 and 2 (8 and 5 investigations) were considered as two grades of preserved AR, and the third one (3 cases) as impaired AR. AVDO2 method: 12 studies were evaluated. 10 showed preserved AR, and 2 impaired AR. There was coincidence of results from both methods in 10 out of 12 studies. (0.83).

Introduction: patients with hematologic malignancies (HM) admitted in intensive care units (ICU) have been traditionally seen as patients with very poor prognostic. Recently reports have informed that mortality has dropped and nowadays is in the order of 40-60 %, this is still high but closer to mortality in non-malignant patients admitted in an ICU. In an attempt to change this view we perform a study in order to evaluate the results and prognostic factors that contribute to mortality in HM patients who need critical care assistance. Methods: a retrospective study in 62 patients with HM who were admitted in ICU in the University Hospital, Hospital de Clinicas from Uruguay from 2003 to 2012. These 62 patients had 82 admissions, which are the population of our trial. Statistical analysis: Values are expressed as mean +/- standard deviation (SD), median and percentages. Comparison variable most used: discharge of ICU: dead or alive. Both groups were compared using Student's t test and Chi square. Multivariate logistic regression analysis was performed. Overall survival with Kaplan Meier. Significance p

Traumatic brain injury initiates several metabolic processes that can increase the primary injury. It is well established that in severe head injuries, posttraumatic secondary insults, such as brain hypoxia, hypotension or anemia, exacerbate neuronal injury and lead to a poorer outcome. Experimental and clinical evidence suggests that moderate hypothermia (32-34 degrees C), may limit some of these deleterious secondary metabolic responses. Recent laboratory studies and prospective controlled clinical trials of induced moderate hypothermia for relatively short periods (24-48 h) in patients with severe head injury, have demonstrated good intracranial pressure control and better outcome when compared with patients maintained in normothermia and given conventional treatment. Despite its proven clinical role in neuroprotection, hypothermia research has been inconstantly followed for various reasons. In this paper we review the mechanisms of neuroprotection in hypothermia, the different preclinical and clinical studies that favor its use as a neuroprotector in severe head injury or in patients in whom high intracranial pressure is refractory to first tier measures. The evidence that favors hypothermia is discussed. We also discuss the negative results of the still unpublished multicentre trial on prophylactic moderate hypothermia developed in the USA. The main problem with moderate hypothermia is the lack of a systematic methodology to induce and maintain it. Also, optimal duration of its use and the methodology and timing for rewarming have not been determined. Consequently, the results of different trials are difficult to analyze and compare. However, most evidence suggests that hypothermia provides remarkable protection against the adverse effects of neuronal damage that is exacerbated by secondary injury. Further prospective controlled trials with clearly defined methodology are needed before this method is implemented in daily clinical practice. The most important task for the years to come may be to focus on refining this procedure, defining the optimal time of cooling and rewarming and to optimize the methods of rapidly inducing and maintaining low temperature. It is also essential to define the most appropriate method and velocity of the rewarming phase, in which many successfully controlled patients deteriorate and die.

Cerebral ischemia due to low cerebral perfusion pressure (CPP) is the most important secondary effect of severe head injury. There is consensus regarding the maintenance of this pressure at levels above 70 mm Hg. One way to elevate CPP is by increasing mean arterial pressure (MAP). In this study, the authors attain this target by using adrenergic vasopressors investigating the effectiveness of dopamine, noradrenaline and methoxamine in 16 severe head injured patients. The results were: a) the increase of MAP effectively increased CPP without changes in intracranial pressure (ICP) and cerebral extraction of oxygen (CEO2); b) noradrenaline at a dose of 0.5 mg to 5 mg/h was effective and safe and might be considered the drug of choice; c) dopamine was not as effective at a high dose of 10 to 42.5 micrograms/kg/min; d) methoxamine given as a bolus was an effective way to control sudden decreases in MAP. It made the patients more responsive to dopamine. No important undesirable reactions occurred during the study.

Cerebral ischemia due to low cerebral perfusion pressure (CPP) is the most important secondary effect of severe head injury. There is consensus regarding the maintenance of this pressure at levels above 70 mm Hg. One way to elevate CPP is by increasing mean arterial pressure (MAP). In this study, the authors attain this target by using adrenergic vasopressors investigating the effectiveness of dopamine, noradrenaline and methoxamine in 16 severe head injured patients. The results were: a) the increase of MAP effectively increased CPP without changes in intracranial pressure (ICP) and cerebral extraction of oxygen (CEO2); b) noradrenaline at a dose of 0.5 mg to 5 mg/h was effective and safe and might be considered the drug of choice; c) dopamine was not as effective at a high dose of 10 to 42.5 micrograms/kg/min; d) methoxamine given as a bolus was an effective way to control sudden decreases in MAP. It made the patients more responsive to dopamine. No important undesirable reactions occurred during the study.