Acute Hypotension Research Articles

Thrombolytic Therapy for Pulmonary Embolism: Lessons from Recent Clinical Trials

Pulmonary embolism is a common disease that is associated with significant mobility and mortality. Thrombolysis is potentially life saving when used in conjunction with anticoagulant therapy. Indications for thrombolysis for pulmonary embolism are not well defined. In patients with acute massive pulmonary embolism and hypotension, thrombolytic therapy offers some benefits in terms of mortality reduction. The use of thrombolysis in patients with stable haemodynamics has been controversial for more than two decades. Recent clinical studies have indicated that thrombolytic treatment in conjunction with heparin in patients with submassive pulmonary embolism and normal blood pressure can prevent deterioration of the disease and diminish the need for more intensive therapies during hospitalisation. The role of prehospital thrombolytic therapy for acute pulmonary embolism is unclear and further clinical studies are warranted.

3. Internationales Symposium: „Autologe Transfusion - Von der Euphorie zur Ratio: Praktisches Handeln aus wissenschaftlicher Sicht” (Teil II)Autologe Transfusion bei Kindern - Fremdblutsparende Verfahren

It is uncontested that blood-saving strategies should also be applied in children. However, in the past, blood-saving techniques saw limited use in children, although they are well-established in adults. This is due to technical and methodical problems, but also to the physiologically limited compensatory mechanisms for diminished oxygen delivery in this age group. For this reason, the various blood saving-techniques cannot be universally applied to all age groups. During the first year of life most perioperative techniques are of only limited benefit: even only a small amount of blood loss in relation to total blood volume makes a transfusion of allogeneic blood necessary, which is far before enough shed blood can be recovered for retransfusion. Preoperative autologous donation of blood calls for a high degree of cooperation by the child and the parents an is equally demanding in terms of organization and skills. Therefore, this procedure is used mainly in school-age children and in adolescents. Intraoperative blood salvage, by contrast, is already worthwhile in children from age one year with an expected blood loss of 20 % of blood volume. Acute normovolemic hemodilution and deliberate hypotension should be recommended only in an age group where cardiovascular compensatory mechanisms are given. Supporting procedures aimed at avoiding the need for allogeneic blood include perioperative administration of erythropoietin, iron supplementation, blood-saving surgical techniques and careful hemostasis. These prerequisites, the combination of various techniques, as well as the definition of an age-specific low transfusion trigger have contributed to a marked decrease in the need for allogeneic blood products in children in recent years.

Adaptive Predictive Control of Arterial Blood Pressure Based on a Neural Network During Acute Hypotension

In acute hypotension, an automated drug infusion system to control mean arterial blood pressure (MAP) has not been previously studied, though many investigations have examined the use of vasodilating drugs to control MAP in postoperative hypertension. Therefore, we examined an automated control of MAP during acute hypotension using a neural network (NN) approach. A proportional-integral-derivative (PID) control, an adaptive predictive control using a NN (APC(NN)), a combined control of APC(NN) and PID (APC(NN-PID)), a fuzzy control, and a model predictive control were tested in computer simulation based on the MAP response to norepinephrine (NE) of 25 microg ml(-1). In six anesthetized rabbits, using the NE of 25 microg ml(-1), the PID control, APC(NN), and APC(NN-PID) prevented severe hypotension compared to an uncontrolled condition. Under PID control, four of the six animals showed MAP oscillation. Using NE of 50 microg ml(-1), the rabbits recovered from acute hypotension for all systems tested but showed sustained MAP oscillation during PID control. In conclusion, utilization of a NN for adaptive predictive control systems could facilitate the development of an automated drug infusion apparatus because it provides robust control even when acute or large perturbations and inter-individual differences in the sensitivity to therapeutic agents occur.

Hypotension and acute pulmonary insufficiency following transfusion of autologous red blood cells during surgery: a case report and review of the literature

Transfusion of autologous blood is associated with fewer complications, although all untoward events of transfusion may not be negated with this strategy. We report a case of acute pulmonary insufficiency and hypotension following transfusion of autologous packed red blood cells (PRBCs) in a patient, who was undergoing major surgery. Anti-HLA class-I and class-II and anti-granulocyte antibodies were measured in the unit and in the recipient. Neutrophil (PMN)-priming activity was measured as the augmentation of the formyl-Met-Leu-Phe-activated respiratory burst. No immunoglobulins were identified; however, significant lipid-priming activity was present in the implicated, autologous PRBC unit that primed PMNs from both healthy people and the recipient. In addition, lipids, identical to those that accumulate during PRBC storage, caused significant hypotension when infused into rats at similar concentrations found in stored PRBCs. We conclude that the observed transfusion-related acute lung injury reaction with significant hypotension may be the result of two independent events: the first is related to inherent host factors, in this case major surgery, and the second is the infusion of lipids that accumulate during the routine storage of PRBCs.

Adaptive predictive control using a neural network in acute hypotension

We examined a mean arterial blood pressure (MAP) control during acute hypotension using a neural network (NN). A proportional-integral-derivative (PID) control, an adaptive predictive control using a NN (APCNN), and a combined control of APCNN and PID (APCNN-PID) were tested. In anesthetized rabbits, using the NE of 25 µg ml-1, the PID control, APCNN and APCNN-PID prevented severe hypotension. Using NE of 50 µg ml-1, the rabbits recovered from acute hypotension for all systems tested but showed sustained MAP oscillation during PID control. Utilization of a NN for adaptive predictive control systems could facilitate the development of a drug infusion apparatus.

Effect of subcutaneous amifostine administration on systolic blood pressure in patients receiving daily fractionated radiotherapy

8176 Background: Acute hypotension is recognized as a potential complication of intravenous and subcutaneous amifostine administration. This study was undertaken to assess the degree and severity of changes in systolic blood presssure (SBP) after the daily subcutaneous administration of 500mg of amifostine prior to the delivery of fractionated external beam radiotherapy. Methods: From 03/2002 through 03/2003, 20 patients with primary head and neck (12) or non-small cell lung (8) cancers received a total of 350 subcutaneous amifostine administrations. Patients received a mean of 17.5 and a median of 18 doses over their planned course of radiotherapy. Patients were advised to consume 16 ounces of water or other clear liquid two hours prior to amifostine administration. Patients were advised to continue their previously prescribed blood pressure medications. Blood pressure readings were taken prior to each injection. The injection of amfostine was withheld if SBP was felt to be inadequate. Three follow up blood pressure readings were taken within 30 minutes after the subcutaneous injections. Results: No patient suffered a significant hypotensive episode requiring IV fluid administration or other remedial intervention. Mean and median SBP declines were 12.4mmHg and 12mmHg respectively for all injections delivered. The greatest single decline in SBP seen was 42mmHg, however 90% of all declines in SBP were less than 25mmHg. Conclusions: The current study demonstrates the safety and feasibility of subcutaneous amifostine administration in the setting of daily fractionated radiotherapy. The data presented may be used to roughly predict the expected post-injection SBP in patients receiving subcutaneous amifostine in this dose range. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Mediumne (Nichols)

Effect of subcutaneous amifostine administration on systolic blood pressure in patients receiving daily fractionated radiotherapy

8176 Background: Acute hypotension is recognized as a potential complication of intravenous and subcutaneous amifostine administration. This study was undertaken to assess the degree and severity of changes in systolic blood presssure (SBP) after the daily subcutaneous administration of 500mg of amifostine prior to the delivery of fractionated external beam radiotherapy. Methods: From 03/2002 through 03/2003, 20 patients with primary head and neck (12) or non-small cell lung (8) cancers received a total of 350 subcutaneous amifostine administrations. Patients received a mean of 17.5 and a median of 18 doses over their planned course of radiotherapy. Patients were advised to consume 16 ounces of water or other clear liquid two hours prior to amifostine administration. Patients were advised to continue their previously prescribed blood pressure medications. Blood pressure readings were taken prior to each injection. The injection of amfostine was withheld if SBP was felt to be inadequate. Three follow up blood pressure readings were taken within 30 minutes after the subcutaneous injections. Results: No patient suffered a significant hypotensive episode requiring IV fluid administration or other remedial intervention. Mean and median SBP declines were 12.4mmHg and 12mmHg respectively for all injections delivered. The greatest single decline in SBP seen was 42mmHg, however 90% of all declines in SBP were less than 25mmHg. Conclusions: The current study demonstrates the safety and feasibility of subcutaneous amifostine administration in the setting of daily fractionated radiotherapy. The data presented may be used to roughly predict the expected post-injection SBP in patients receiving subcutaneous amifostine in this dose range. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Mediumne (Nichols)

Acute hypotension induced by aortic clamp vs. PTH provokes distinct proximal tubule Na+ transporter redistribution patterns.

Renal parathyroid hormone (PTH) action is often studied at high doses (100 microg PTH/kg) that lower mean arterial pressure significantly, albeit transiently, complicating interpretation of studies. Little is known about the effect of acute hypotension on proximal tubule Na(+) transporters. This study aimed to determine the effects of acute hypotension, induced by aortic clamp or by high-dose PTH (100 microg PTH/kg), on renal hemodynamics and proximal tubule Na/H exchanger isoform 3 (NHE3) and type IIa Na-P(i) cotransporter protein (NaPi2) distribution. Subcellular distribution was analyzed in renal cortical membranes fractionated on sorbitol density gradients. Aortic clamp-induced acute hypotension (from 100 +/- 3 to 78 +/- 2 mmHg) provoked a 62% decrease in urine output and a significant decrease in volume flow from the proximal tubule detected as a 66% decrease in endogenous lithium clearance. There was, however, no significant change in glomerular filtration rate (GFR) or subcellular distribution of NHE3 and NaPi2. In contrast, high-dose PTH rapidly (<2 min) decreased arterial blood pressure to 51 +/- 3 mmHg, decreased urine output, and shifted NHE3 and NaPi2 out of the low-density membranes enriched in apical markers. PTH at much lower doses (<1.4 microg.kg(-1).h(-1)) did not change blood pressure and was diuretic. In conclusion, acute hypotension per se increases proximal tubule Na(+) reabsorption without changing NHE3 or NaPi2 subcellular distribution, indicating that trafficking of transporters to the surface is not the likely mechanism; in comparison, hypotension secondary to high-dose PTH blocks the primary diuretic effect of PTH but does not inhibit the PTH-stimulated redistribution of NHE3 and NaPi2 to the base of the microvilli.

Effects of Dialysis Technique on Acute Hypotension: A Model-Based Study

The patient's tendency to develop acute hemodialysis-induced hypotension can be influenced by the choice of hemodialysis technique (dialysate composition, filter, convection/diffusion ratio, etc.). We examined the hypothesis that the dialysis technique affects the pressure behavior during the sessions complicated by hypotension by altering the short-term compensatory reflexes to hemodialysis-induced hypovolemia. Hypotension-prone subjects were studied both during sessions of conventional bicarbonate dialysis (BD) and during sessions of acetate-free biofiltration (AFB) complicated by hypotension (8 BD vs 8 AFB). (a) During BD hypotension occurred, on average, about 70 min earlier than in AFB treatments (hypotension time: 120 ± 66 min in BD vs 193 ± 26 min in AFB, p < 0.01), and (b) patients exhibited a major susceptibility to blood volume reduction (blood volume reduction at hypotension time: −7.17 ± 3.26% in BD vs −10.88 ± 2.46% in AFB, p < 0.05). A mathematical model was used to analyze the efficacy of reflex compensatory mechanisms during hemodialysis sessions. Data analysis using the model indicated that during BD sessions all the compensatory mechanisms were almost inoperative, whereas during the AFB sessions residual compensatory reflexes were active. Model simulation demonstrated that hypotension occurred later in AFB because the residual compensatory capacity in AFB was able to maintain arterial pressure for higher blood volume reductions.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Cerebral ischaemia during cardiac surgery in children detected by combined monitoring of BIS and near-infrared spectroscopy

Children frequently suffer transient cerebral ischaemia during cardiac surgery. We measured cerebral ischaemia in children during cardiac surgery by combining two methods of monitoring. We studied 65 children aged between 5 months and 17 yr having surgery to correct non-cyanotic heart disease using hypothermic cardiopulmonary bypass (CPB). During surgery, we measured the Bispectral Index (BIS) and regional cerebral haemoglobin oxygen saturation (SrO2) with near-infrared spectroscopy (NIRS). Cerebral ischaemia was diagnosed if both SrO2 and BIS decreased abruptly when acute hypotension occurred. In each patient, the relationship between SrO2 and arterial blood pressure (AP) was indicated by a plot of mean SrO2 against simultaneous mean AP. We noted 72 episodes of cerebral ischaemia in 38 patients. Sixty-three ischaemic events were during CPB. Cerebral ischaemia was less frequent in older patients. Cerebral ischaemia was more common and more frequent in children under 4 yr old. Haematocrit during CPB was lower and SrO2 was more dependent on AP in children under 4 yr. Children less than 4 yr of age are more likely to have cerebral ischaemia caused by hypotension during cardiac surgery. Ineffective cerebral autoregulation and haemodilution during CPB may be responsible.

Immunohistochemical detection of phosphorylated form of extracellular signal-regulated kinase 1/2 in rat vestibular nuclei following hemorrhagic hypotension

The purpose of this study was to evaluate the expression of the phosphorylated form of extracellular-regulated protein kinase 1/2 (pERK1/2), which is one of the major regulatory factors for transcription of the c-fos oncogene in neurons, within the vestibular nuclei (VN) of rats following acute arterial hypotension. Following acute arterial hypotension induced by rapid hemorrhage, a significant number of pERK1/2-immunoreactive neurons appeared bilaterally in the caudal aspect of the medial and inferior VN. No labeling of pERK1/2 was observed in the lateral VN. The peak expression of pERK1/2-immunoreactive neurons in these nuclei occurred within 5 min after hemorrhage. In bilaterally labyrinthectomized rats, the appearance of pERK1/2-immunoreactive neurons was eliminated in the VN. These results suggest that, following acute hypotension, afferent signals from the peripheral vestibular receptors are required for activation of extracellular signal-regulated kinase 1/2 in the VN.

Model-based study of the effects of the hemodialysis technique on the compensatory response to hypovolemia

Hemodialysis technique (dialysate composition, filter, convection/diffusion ratio, etc.) can have an impact on the patient's tendency to acute hypotension. We have examined the hypothesis that the dialysis technique affects the hypotension risk by altering the cardiovascular compensatory response to hemodialysis-induced hypovolemia. Twelve hypotension-prone subjects were studied during six sessions of conventional bicarbonate dialysis (BD) and six sessions of acetate-free biofiltration (AFB). Blood volume (BV) control system was used in AFB to provide a BV change equivalent to the BV change observed in BD. The efficacy of reflex compensatory mechanisms was assessed by a model-based computer analysis of the BD and AFB sessions. BD sessions were complicated by hypotension more frequently than the AFB ones (34/66 BD vs. 18/66 AFB). Hypotension arose about 60 minutes earlier in BD (123 +/- 41 minutes in BD vs. 183 +/- 25 minutes in AFB, P < 0.01), and after a smaller BV reduction (hypotension BV 7.9%+/- 2.0% in BD vs. 10.9%+/- 2.6% in AFB, P < 0.05). Model-based computer analysis of the sessions without hypotension revealed differences in peripheral resistance adaptation (9%+/- 9% BD vs. 19%+/- 7% AFB, P < 0.05) as well as in the stroke volume reduction (19%+/- 8% BD vs. 10%+/- 8% AFB, P < 0.001). Model analysis of sessions with hypotension indicated that compensatory mechanisms were almost inoperative in BD, whereas a residual capacity to control peripheral resistance and cardiac contractility was present in AFB. Model simulations demonstrated that hypotension occurred later in AFB since the residual compensatory capacity in AFB was able to sustain the arterial pressure for larger BV reductions (8.3% BD vs. 11.2% AFB). The increased risk of acute hypotension in BD compared to AFB is caused by a therapy-induced inhibition of reflex compensatory response to hypovolemia.

Major Ongoing Stroke Trials

Major Ongoing Stroke Trials

Diplopia: a complication of dural puncture.

Diplopia: a complication of dural puncture.

Importance of calcitonin gene-related peptide, adenosine and reactive oxygen species in cerebral autoregulation under normal and diseased conditions.

1. Mechanisms regulating cerebral circulation, including autoregulation of cerebral blood flow (CBF), have been widely investigated. Vasodilators such as nitric oxide, prostacyclin, calcitonin gene-related peptide (CGRP) and K+ channel openers are well known to have important roles in the physiological and pathophysiological control of CBF autoregulation. In the present review, the focus is on the mechanism(s) of altered CBF autoregulation after traumatic brain injury and subarachnoid haemorrhage (SAH) and on the effect of adenovirus-mediated transfer of Cu/Zn superoxide dismutase (SOD)-1 in amelioration of impaired CBF autoregulation. 2. The roles of CGRP and adenosine are particularly emphasized, both being implicated in the autoregulatory vasodilation of the pial artery in response to hypotension. 3. After fluid percussion injury, production of NADPH oxidase-derived superoxide anion and activation of tyrosine kinase links the inhibition of K+ channels to impaired autoregulatory vasodilation in response to acute hypotension and alterations in CBF autoregulation in rat pial artery. 4. Subarachnoid haemorrhage during the acute stage causes an increase in NADPH oxidase-dependent superoxide formation in cerebral vessels in association with activated tyrosine phosphorylation-coupled increased expression of gp91phox mRNA and membrane translocation of Rac protein, thereby resulting in a significant reduction of autoregulatory vasodilation. 5. Fluid percussion injury and SAH-induced overproduction of superoxide anion in cerebral vessels contributes to the impairment of CBF autoregulation and administration of recombinant adenovirus-mediated transfer of the Cu/Zn SOD-1 gene effectively ameliorates the impairment of CBF autoregulation of the pial artery.

Loveless on wasp venom allergy and immunity. Part 2. The contribution of Dr Mary Hewitt Loveless to the management of allergy to insect stings

Loveless on wasp venom allergy and immunity. Part 2. The contribution of Dr Mary Hewitt Loveless to the management of allergy to insect stings

Membrane pore size impacts performance of a xenogeneic bioartificial liver.

We have developed a novel bioartificial liver (BAL) composed of porcine hepatocyte spheroids in a reservoir design. A semipermeable membrane is used to protect the spheroids from immune-mediated damage. This study was designed to assess the influence of membrane pore size on performance of the spheroid reservoir BAL. Eight healthy dogs were studied during primary and secondary exposures to the spheroid reservoir BAL using membranes with small (10 nm) or large (200 nm) pores. BAL performance was assessed by multiple functional assays. Spheroids were examined microscopically before and after all BAL treatments. Titers of xenoreactive antibody were monitored until elective death of animals on day 42. Viability and functional performance of spheroids were significantly greater after all BAL treatments that used membranes with 10-nm versus 200-nm pores. Reduced performance in the 200 nm group was associated with 7.7-fold and 78.0-fold rise in xenoreactive antibody titers after first and second treatments, respectively. Dogs in the 10 nm group remained hemodynamically stable during all BAL treatments, whereas those in the 200 nm group experienced acute hypotension (P<0.001) during second BAL exposures. Microscopic examination of spheroids after BAL treatments indicated that deposition of canine proteins, including complement, was associated with reductions in both viability and functional performance of the BAL. The elicited immune response of healthy dogs to a xenogeneic BAL was blocked and BAL performance significantly improved by reducing the permeability of the BAL membrane.

Haemodynamic and metabolic disturbances in the acute stage of subarachnoid haemorrhage demonstrated by PET.

To investigate the occurrence of early haemodynamic and metabolic changes in the acute stage of subarachnoid haemorrhage (SAH). Eleven SAH patients were studied. Regional cerebral blood flow (CBF), cerebral metabolic rate of oxygen (CMRO2) and oxygen extraction ratio (OER) were measured with positron emission tomography (PET) 22-53 h after haemorrhage, utilizing 15O-labelled water bolus and the 15O-inhalation technique. Ten volumes of interest (VOIs) representing vascular territories were outlined in each patient according to a standardized procedure. The occurrence of irreversible ischaemia, penumbra, oligaemia, hyperperfusion and normal haemodynamics according to PET criteria was investigated. These pathophysiological categories were related to final tissue outcome as determined by follow-up computed tomography (CT). All five tissue subtypes were represented in the vascular region VOIs; oligaemia was the predominant pathophysiological pattern. When global changes were analysed, blood flow was reduced in three, oxygen metabolism was reduced in four, and OER was increased in four of seven unsedated patients, respectively. The sedated patients all had markedly reduced CBF and CMRO2 and OER in the high or supranormal range. Haemodynamic and metabolic disturbances proved to be common after SAH. These abnormalities probably reflect the primary brain injury caused by the initial haemorrhage. The impact of secondary insults such as acute hydrocephalus, brain oedema, vasospasm, seizures, hypotension and hypoxaemia are likely to be dependent on the degree of primary injury, which can be assessed by PET.

Cardiovascular Changes During Multiple Vertebroplasty With and Without Vent-Hole

An experimental study of cardiovascular complications arising during vertebroplasty (VP) of multiple levels. To investigate the cardiovascular changes during multiple VP and whether a vent-hole has a preventive effect. An experimental study and clinical reports showed that fat embolism (FE) and acute hypotension occur during VP. There is the concern that these complications may worsen during VP of multiple levels. Vent-holes may prevent FE during VP. In twenty-two sheep, four vertebral bodies were augmented with polymethylmethacrylate (PMMA). In ten sheep, a vent-hole was drilled into the pedicle contralateral to the injection site. Heart rate, arterial, central venous and pulmonary artery pressure, cardiac output and blood gas values were recorded. The lungs were subjected to histologic evaluation at postmortem. The consecutive augmentation of four vertebral bodies with PMMA induced a cumulative FE that gradually deteriorated baseline mean arterial blood pressure (MABP) and blood gas values. The deterioration of MABP and change in blood gas values were attenuated, when a vent-hole was drilled. The amount of intravascular fat in the lungs after multiple VP (19%) was reduced when a vent-hole was drilled (9%). Surgeons should be aware of the potential cardiovascular complications during VP of multiple levels. In the clinical setting, a needle in the contralateral pedicle could be used to decompress the vertebral body during the injection of bone cement.