M. Heesen

The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically III patients

Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient.The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2 I), and oxygen delivery index (DO (2) I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2 I, and DO2 I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (<40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (>7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pHi decreased (<7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy. (Anesth Analg 1996;83:254-61)

Influence of different volume therapies on platelet function in the critically ill

ObjectiveBoth albumin and synthetic colloids such as hydroxyethyl starch (HES) solution are used to optimize hemodynamics in the critically ill. The influence of different long-term infusion regimes on platelet function was studied.DesignProspective, randomized study.SettingClinical investigation on a university hospital surgical intensive care unit.PatientsTwenty-eight consecutive trauma patients (injury severity score>15 points) and 28 consecutive nontraumatized surgical patients with sepsis.InterventionsThe patients received either 20% human albumin (HA trauma,n=14; HA sepsis,n=14) or 10% low-molecular-weight HES solution HES 200/0.5 (HES trauma,n=14; HES sepsis;n=14) for 5 days to maintain central venous pressure and/or pulmonary capillary wedge pressure between 12 and 16 mmHg.Measurements and resultsPlatelet function was assessed by aggregometry (=turbidimetric technique) using adenosine diphosphate 2.0 μmol/l, collagen 4 μl/ml, and epinephrine 25 μmol/l as inductors. Arterial blood was sampled on the day of admission or the day of diagnosis of sepsis (=baseline value) and over the next 5 days. Standard coagulation parameters (antithrombin III, fibrinogen, partial thromboplastin time) were also measured. Total use of HES by the 5th day totalled 4870±990 ml in the trauma and 3260±790 ml in the sepsis patients (HA trauma: 1850±380 ml; HA sepsis: 1790±400 ml). Maximum platelet aggregation decreased significantly during the first 2–3 days after baseline in all groups. At the end of the investigation period, platelet aggregation variables had recovered and reached (or even exceeded) baseline values. Within the entire investigation period, the course of platelet aggregation variables did not differ significantly between HA and HES-treated patients irrespective of whether they were trauma or sepsis patients.ConclusionsAlterations in hemostasis may occur for several reasons in the critically ill. Human albumin is the preferred first-line volume therapy in patients at risk for coagulation disorders. With respect to platelet function, volume replacement with (lower-priced) low-molecular-weight HES solutions can be recommended in this situation without any risk.

The influence of volume therapy and pentoxifylline infusion on circulating adhesion molecules in trauma patients

Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process. Besides neutrophiland endothelial‐bound adhesion molecules, soluble forms have been detected in the circulating blood. They seem to be good markers of endothelial damage, but they may also have other biological functions. Plasma concentrations of soluble adhesion molecules (endothelial leucocyte adhesion molecules (sELAM‐1), intercellular adhesion molecule‐1 (sICAM‐1), vascular cell adhesion molecule‐1 (sVCAM‐1), and granule membrane protein 140 (sGMP‐140) were serially measured over 5 days by enzyme‐linked immunosorbent assays (ELISA) in 45 consecutive trauma patients. These received, by random allocation, only either hydroxyethylstarch solution 10% (mean molecular weight 200 000 daltons) (n = 15) or human albumin 20% (n = 15) for volume therapy. Another 15 patients without defined volume therapy received pentoxifylline continuously (1.2mg.kg‐1.h‐1). Measurements were carried out on the day of admission to the intensive care unit (baseline) and during the next 5 days. At baseline, plasma concentrations of all adhesion molecules were similar in all groups. In the hydroxyethyl starch group, sELAM‐1 and sICAM‐1 concentrations decreased significantly (p < 0.05) reaching normal values during the study period whereas the mean (SD) values increased in the pentoxifylline group (sELAM‐1: 71.1 (16.7) to 91.6 (17.8) ng.ml‐1) and the albumin group (sICAM‐1: 400 (81) to 749 (101) ng.ml‐1) (p < 0.05). sVCAM‐1 increased outside the normal range only in the human albumin group (to 760 ± 69 ng.ml‐1) (p < 0.05). sGMP‐140 plasma concentration increased only in those receiving albumin (432 (85) to 550 (93) ng.ml‐1) and this was significantly different to the other groups (p < 0.05). None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules. We conclude that colume therapy with hydroxyethyl starch resulted in a decrease in circulating adhesion molecules in our trauma patients. In contrast, volume therapy with albumin did not exert this effect. Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules.

Increase of interleukin-6 plasma levels after elective craniotomy: Influence of interleukin-10 and catecholamines

SummaryAccidental and operative trauma are able to induce a systemic reaction of the organism characterized by fever, leukocytosis, catabolism, and an activation of the coagulation system. Interleukin-6 (IL-6) has been found to be an important mediator of this acute-phase response. In this study the influence of elective craniotomy on IL-6 plasma levels was evaluated. Blood samples were obtained from 20 patients undergoing elective craniotorny for vascular or tumorous diseases of the brain. IL-6 increased significantly (p < 0.05) from the pre-operative (0 (0–5.4) pg/ml) to the intraoperative (180 min after beginning of surgery) time-point (10.6 (0–18.5) pg/ml). The maximum was reached on the first postoperative morning (13.9 (4.3–45.0) pg/ml). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which suppresses IL-6 synthesis in vitro in various cell lines. IL-10 plasma concentrations showed no alterations throughout the study period. Epinephrine plasma concentrations increased significantly from pre-operative values (15 (0–74) pg/ml) to the postoperative time-point (57 (9–459) pg/ml). A 4.5-fold increase (p < 0.05) of norepinephrine plasma concentrations was found when comparing the data obtained 60 min after beginning of surgery with the data of the first postoperative morning. In monocytes, which are a major source of plasma IL-6, an elevation of intracellular cAMP stimulates the IL-6 synthesis. The postoperative maximum of IL-6 in plasma could be due to a release of catecholamines. In conclusion this study demonstrated an elevation of IL-6 plasma concentrations during and after elective craniotomy. Increased plasma catecholamine concentrations as well as a damage in the blood-brain barrier due to the surgical trauma with a spill-over of IL-6 from brain tissue into plasma could have contributed to this result.

Platelet Function and Adrenoceptors during and after Induced Hypotension using Nitroprusside

Background Hypotension induced by sodium nitroprusside can minimize intraoperative blood loss. The release of endogenous catecholamines can influence adrenoceptors of platelets and thus might change the ability of platelets to aggregate. Methods Forty patients undergoing nasal septum, tympanoplastic, or sphenoid sinus surgery were randomly divided into two groups, those having controlled hypotension (A) and those serving as controls (B). Blood samples were drawn before the operation, after induction of anesthesia, 1 h after the start of the operation, and on the day after surgery. Results Epinephrine-induced platelet aggregation only increased in the controls on the day after surgery (A: from 49 +/- 25% to 47 +/- 29%; B: from 53 +/- 24% to 72 +/- 14%; mean +/- SD; P < 0.01). Spontaneous platelet aggregation increased in the controls from a median of 1.2 Ohm/h to 2.4 during the operation and 2.9 on the day after surgery but not after hypotension. On the day after surgery, alpha2 receptors reached their maximum (A: 238 +/- 164; B: 234 +/- 80 per platelet). During the operation, the norepinephrine concentrations were significantly greater in group A (median, 419 pg/ml) than in group B (median, 217 pg/ml; P < 0.05). Blood loss was greater in the controls (A: 180 +/- 75; B: 379 +/- 120 ml; P < 0.05). Conclusions Controlled hypotension using sodium nitroprusside reduces epinephrine-induced and spontaneous platelet aggregation. Even on the day after hypotension, the usual postoperative reactive increase in platelet aggregation did not occur. These results may be explained by the direct effect of nitroprusside on platelets, the augmented stress response, lower shear stress on platelets due to the lower blood pressure, or the decreased blood loss compared with the controls.

Somatosensory Evoked Potential Monitoring during Positioning of the Patient for Posterior Fossa Surgery in the Semisitting Position

OBJECTIVE Midcervical flexion myelopathy is a rare but well-known complication of posterior fossa surgery. To reduce the risk, we routinely used somatosensory evoked potential (SSEP) monitoring during positioning of the patient. METHODS Fifty-five consecutive patients were operated on for posterior fossa lesions in the semisitting position via a median (5 patients) or a lateral (50 patients) suboccipital approach. During positioning, monitoring of SSEPs by stimulation of the tibial nerve (T-SSEP) as well as by stimulation of the median nerve (M-SSEP) was established. In the case of pronounced SSEP changes, the head was repositioned. Surgery was started after SSEP recordings were unchanged as compared to the baseline investigation. RESULTS Effective monitoring was possible in all cases. Whereas M-SSEP recordings showed no changes while placing patients in the sitting position, T-SSEP recordings were altered in 14 cases (25%). In cases using the midline approach, SSEP changes were never so pronounced to require repositioning of the head. Head flexion and rotation resulted in significant changes of T-SSEP recordings in eight patients (14.5%), requiring repositioning. In two cases, an amplitude loss was noted. In only two of these eight patients were M-SSEP recordings markedly changed. SSEP recordings after repositioning disclosed recovery of spinal cord function. In no patient were clinical signs of myelopathy observed postoperatively. CONCLUSION We observed a high incidence of pronounced changes of T-SSEP recordings when the patients head was flexed and rotated for lateral suboccipital craniotomy in the semisitting position. Despite the low specificity monitoring of T-SSEPs during positioning of the patient for posterior fossa surgery, the semisitting position is strongly recommended.

Coagulation alterations in patients undergoing elective craniotomy

BACKGROUND Thromboembolism remains a major problem in patients scheduled for craniotomy. The present study examined parameters of coagulation and fibrinolysis in 15 patients undergoing elective craniotomy in the perioperative period. METHODS Plasma concentrations of thrombin antithrombin III complex (TAT), prothrombin fragment 1 + 2 (F1 + 2), and d-dimer were measured before and after induction of anesthesia, 60 minutes and 180 minutes after the beginning of surgery, and on the first postoperative morning. RESULTS TAT, a marker of activation of coagulation, increased significantly (p < 0.05) from the preoperative measurements to the data obtained 60 minutes after beginning the surgery, reaching a maximum of 180 minutes after the start of surgery. F1 + 2, also indicating activation, showed a similar concentration time course with an intraoperative maximum. D-dimer, a marker of fibrinolysis, tended to increase slightly beginning 180 minutes after surgery with a maximum on the morning after surgery. Statistical significance for F1 + 2 and d-dimer was not found. CONCLUSIONS This study showed a transient activation of coagulation with an intraoperative maximum in patients undergoing craniotomy. This result could be due to a liberation of thromboplastin from brain tissue.

Does age influence circulating adhesion molecules in the critically ill

OBJECTIVE Soluble adhesion molecules are regarded to be markers of inflammation, endothelial activation, or damage. The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients. DESIGN Prospective and descriptive study over 5 days. SETTING Clinical investigation in a surgical intensive care unit of a university hospital. PATIENTS Thirty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] II score of > 15 points), with sepsis secondary to postoperative complications, were included in this study. Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospectively studied. INTERVENTIONS All patients were treated by the standard protocols of our intensive care unit, which did not differ between the groups. The patients received continuous analgesia-sedation and mechanical ventilation. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. MEASUREMENTS AND MAIN RESULTS Hemodynamic parameters were extensively monitored in all patients. From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, granule membrane protein-140) were measured on the day of admission (i.e., baseline values) and during the following 5 days. Three of the younger patients and six of the elderly patients died during the study period (p < .05). Oxygen delivery and consumption, and the other hemodynamic data, were without group differences throughout the study. Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups. These concentrations increased further during the first 2 to 3 days in both groups, with a significantly higher increase in the elderly patients (endothelial leukocyte adhesion molecule-1 to 179 +/- 32 ng/mL; intercellular adhesion molecule-1 to 1695 +/- 158 ng/mL; vascular cell adhesion molecule-1 to 1395 +/- 212 ng/mL; and granule membrane protein-140 to 888 +/- 119 ng/mL). In the younger patients, concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5. In the elderly patients, these concentrations remained significantly higher until the end of the study. CONCLUSIONS The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium. Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules, particularly in the elderly critically ill patient.

The effects of pentoxifylline on circulating adhesion molecules in critically ill patients with acute renal failure treated by continuous veno-venous hemofiltration

ObjectiveCirculating adhesion molecules appear to be excellent markers of endothelial activation in critically ill patients. Pentoxifylline (PTX) may limit sequelae of inflammation and subsequent endothelial activation by various mechanisms. The influence of PTX on the plasma levels of soluble adhesion molecules in critically ill patients undergoing continuous veno-venous hemofiltration (CVVH) was studied.DesignProspective, randomized, blinded study.SettingClinical investigation in the surgical intensive care unit of a university hospital.Patients and participantsFourteen consecutive patients suffering from acute renal failure (ARF) with postoperative complications who received continuous pentoxifylline (CVVH-PTX) i.v. were compared with 14 patients with ARF who did not receive PTX (CVVH control group).InterventionsPump-driven CVVH was carried out with a blood flow ranging from 120 to 150 ml/min. All patients received fentanyl and midazolam continuously and were on mechanical ventilation. PTX (300 mg) was given as a loading dose, followed by continuous infusion of 1.2 mg/kg per h for the next 5 days.Measurements and resultsFrom arterial blood samples, plasma levels of soluble adhesion molecules (endothelial leukocyte adhesion molecules [sELAM-1], and intercellular adhesion molecule-1 [sICAM-1], vascular cell adhesion molecule-1 [sVCAM-1], and P-selectin granule membrane protein [sGMP-140] were measured using enzyme-linked immuno-sorbent assays (ELISA). Measurements were carried out before the start of CVVH to establish baseline values and continued during the next 5 days.Main resultsEleven of the CVVH-PTX patients and 8 of the CVVH control patients survived during the investigation period. In the CVVH-PTX patients 2.4±0.3 g/day of PTX was given. At baseline, plasma levels of sELAM-1, sICAM-1, and sVCAM-1 were markedly higher than normal in both groups. In the CVVH control patients, all measured soluble adhesion molecules increased further during the study period (sELAM-1 from 90±22 to 134±30 ng/ml; sICAM-1 from 958±173 to 1460±209 ng/ml; sVCAM-1 from 1100±188 to 1804 ng/ml; sGM-140 from 499±102 to 688±121 ng/ml) (p<0.05), whereas in the PTX-treated CVVH patients, plasma levels of all soluble adhesion molecules remained almost unchanged. The PaO2/FIO2 increased in the PTX-treated patients (from 209±67 to 282±58 mmHg) and remained almost unchanged in the CVVH control patients.ConclusionLeukocyte/endothelial interactions play an important role in the inflammatory process. Circulating adhesion molecules may serve as markers of the extent of inflammation. Continuous i.v. administration of PTX was successful in blunting the increase of soluble adhesion molecules in critically ill patients undergoing CVVH. Whether these effects result from improved circulation at the microcirculatory level or from (direct or indirect) beneficial effects on endothelial cells warrants further controlled studies.

What the neurosurgeon needs to know about the coagulation system

Intracranial surgery is often complicated by thromboembolic events including the life-threatening pulmonary embolism. After head trauma and in patients with brain tumors disseminated intravascular coagulation (DIC) can occur, characterized by the triggering of the coagulation cascade and the depletion of coagulation factors which ultimately leads to bleeding. The identification of patients at high risk as well as the early diagnosis of hemostatic problems uses routine laboratory parameters such as partial thromboplastin time and prothrombin time reflecting the intrinsic and the extrinsic pathway of the coagulation respectively. Thrombin antithrombin III complexes (TAT) and prothrombin fragment 1 + 2 (F1 + 2) are further indicators of an activation of the coagulation whereas fibrinogen degradation products (FDP) refer to the fibrinolytic system. The basic principles of coagulation and fibrinolysis are summarized as well as the changes of laboratory parameters accompanying DIC, hypercoagulability and hyperfibrinolysis.