[111In]In-CP04 as a novel cholecystokinin-2 receptor ligand with theranostic potential in patients with progressive or metastatic medullary thyroid cancer: final results of a GRAN-T-MTC Phase I clinical trial.

INTRODUCTION: Medullary thyroid cancer (MTC) is a rare malignant tumour of the parafollicular C-cells with an unpredictable clinical course and currently suboptimal diagnostic and therapeutic options, in particular in advanced disease. Overexpression of cholecystokinin-2 receptors (CCK2R) represents a promising avenue to diagnostic imaging and targeted therapy, ideally through a theranostic approach. MATERIALS AND METHODS: A translational study (GRAN-T-MTC) conducted through a Phase I multicentre clinical trial of the indium-111 labelled CP04 ([111In]In-CP04), a CCK2R-seeking ligand was initiated with the goal of developing a theranostic compound. Patients with proven advanced/metastatic MTC or short calcitonin doubling time were enrolled. A two-step concept was developed through the use of low- and high-peptide mass (10 and 50 µg, respectively) for safety assessment, with the higher peptide mass considered appropriate for therapeutic application. Gelofusine was co-infused in a randomized fashion in the second step for the evaluation of potential reduction of the absorbed dose to the kidneys. Imaging for the purpose of biodistribution, dosimetry evaluation, and diagnostic assessment were performed as well as pre-, peri-, and postprocedural clinical and biochemical assessment. RESULTS: Sixteen patients were enrolled. No serious adverse events after application of the compound at both peptide amounts were witnessed; transient tachycardia and flushing were observed in two patients. No changes in biochemistry and clinical status were observed on follow-up. Preliminary dosimetry assessment revealed the highest dose to urinary bladder, followed by the kidneys and stomach wall. The effective dose for 200 MBq of [111In]In-CP04 was estimated at 7±3 mSv and 7±1 mSv for 10 µg and 50 µg CP04, respectively. Administration of Gelofusine reduced the dose to the kidneys by 53%, resulting in the organ absorbed dose of 0.044±0.019 mSv/MBq. Projected absorbed dose to the kidneys with the use of [177Lu]Lu-CP04 was estimated at 0.9±0.4 Gy/7.4 GBq. [111In]In-CP04 scintigraphy was positive in 13 patients (detection rate of 81%) with superior diagnostic performance over conventional imaging. CONCLUSION: In the present study, [111In]In-CP04 was shown to be a safe and effective radiopharmaceutical with promising theranostic characteristics for patients with advanced MTC.

Protective effect of Gelofusine against cRGD-siRNA-induced nephrotoxicity in mice.

Based on successful targeting to the αvß3 integrin of cyclic arginine-glycine-aspartic acid (cRGD), cRGD-conjugated small interfering RNA (siRNA) exhibits tumor targeting and has become a new treatment strategy for solid tumors. However, the nephrotoxicity caused by its renal retention limits its clinical application. Here, we evaluated the protective effect of Gelofusine against cRGD-conjugated siRNA-induced nephrotoxicity in mice. Male Kunming mice (six per group) were either co-injected with Gelofusine and cRGD-siRNA or injected with cRGD-siRNA alone. After administration of these treatments five times, creatinine and blood urea nitrogen (BUN) levels were determined. Hematoxylin-eosin staining (HE staining) and transferase dUTP nick end labeling (TUNEL) analysis were used to compare the difference in renal damage between the groups. Additionally, fluorescence imaging was used to observe the distribution of cRGD-siRNA in vivo. The group co-injected with Gelofusine and cRGD-siRNA displayed lower creatinine and BUN levels than the cRGD-siRNA-alone group and showed less renal damage upon HE staining and TUNEL analysis. Gelofusine decreased the retention time and accelerated the elimination of cRGD-siRNA from the organs, as observed in the fluorescence images. These data indicate that Gelofusine significantly increased the excretion of cRGD-conjugated siRNA and reduced the associated renal damage.

[Efficiency of using gelofusine and voluven in acute normovolemic hemodilution during cardiosurgical interventions].

The aim of the study was to assess the use of gelofusine and voluven for acute normovolemic hemodilution at cardiac surgery under extracorporeal circulation (EC). Sixty-seven patients with coronary heart disease were examined. Heart rate, total peripheral vascular resistance, pulmonary pressure, pulmonary artery wedge pressure, oxygen delivery and consumption, central venous pressure, arteriovenous oxygen difference, oncotic pressure, and postoperative clinical course were studied. No significant group differences were found in indices, other than arteriovenous oxygen difference, after acute normovolemic hemodilution and in central venous pressure following 6 hours of EC termination. The administration of gelofusine caused a more steady-state oxygen-transport function of the circulatory system. The use of the agent for acute normovolemic hemodilution at cardiac surgery under EC is more economically justified than that of volumen.

Hearing loss after spinal anesthesia: the effect of different infusion solutions.

OBJECTIVE: We speculate that the preoperative volume replacement with a convenient solution may protect the inner ear function after spinal anesthesia. METHODS: The patients were randomized in a single-blind fashion into two groups: group LR (n = 40) received lactated Ringer's and group GF (n = 40) received gelatin polysuccinate 4% (Gelofusine). Spinal anesthesia was performed with a 25 G Quincke needle and was given bupivacaine 0.5% 10 mg and fentanyl 25 microg. Audiograms were performed preoperatively and 2 days postoperatively. RESULTS: The overall incidence of hearing loss was 7.5%. The hearing loss was unilateral in two and bilateral in four patients. Hearing loss occurred within the low-frequency range and the hearing thresholds returned to normal by the fifth postoperative day. CONCLUSIONS: Although the incidence of hearing loss for the lactated Ringer's group was higher than the Gelofusine group, there was no statistically significant difference between the groups. For medicolegal and ethical reasons, patients should be informed about the possibility of hearing loss after spinal anesthesia.

Influence of different strategies of volume replacement on the activity of matrix metalloproteinases: an in vitro and in vivo study.

BACKGROUND: Excessive production of matrix metalloproteinase 9 (MMP-9) is linked to tissue damage and anastomotic leakage after large bowel surgery. Hence, the aim of this study was to verify whether different strategies of fluids administration can reduce MMP-9 expression. METHODS: In the in vitro experiment, the authors tested the hypothesis of a direct inhibition of MMP-9 by the fluids used perioperatively, i.e., lactated Ringer's solution, 3.4% poligeline, and hydroxyethyl starch 130/0.4. In the in vivo experiment, 36 patients undergoing surgery for colon cancer were randomly assigned to three groups to receive lactated Ringer's solution, poligeline, or hydroxyethyl starch. MMP-9 and tissue inhibitor of metalloproteinases were measured from venous blood samples; the MMP-9/tissue inhibitor of metalloproteinases ratio was calculated as an index of equilibrium between the action of MMP-9 and its inhibition. RESULTS: In the in vitro experiment, the presence of hydroxyethyl starch 130/0.4 in the MMP-9 assay system showed a strong inhibition of the enzymatic activity compared with lactated Ringer's solution. In the in vivo experiment, MMP-9 and tissue inhibitor of metalloproteinases plasma levels did not differ among the three groups at baseline, whereas those levels increased significantly at the end of surgery. At that time, the MMP-9 plasma levels and the MMP-9/tissue inhibitor of metalloproteinases ratio were significantly higher in the lactated Ringer's solution and poligeline groups than in the hydroxyethyl starch group. These results were confirmed 72 h after surgery. CONCLUSIONS: This study demonstrates that hydroxyethyl starch 130/04 decreases the circulating levels of MMP-9 in patients undergoing abdominal surgery.

Low molecular starch versus gelatin plasma expander during CPB: does it make a difference?

BACKGROUND: Non-protein plasma expanders carry a risk of potentially severe allergic reactions. As prime for cardiopulmonary bypass, we routinely use a gelatin plasma expander. Plasma expanding during anesthesia is achieved with high molecular starch (200/0.5 kDalton) in combination with Ringer Lactate solution (RL) and in the Intensive Care Unit (ICU) with a low molecular starch (130/0.4 kDalton). We evaluated the feasibility of low molecular starch in combination with RL (group LMSRL) versus gelatin plasma expanding (group GPE) for priming CPB circuits in patients undergoing cardiac surgery in a randomized prospective trial. METHODS: One hundred and eighty adults who underwent primary valve or coronary artery bypass graft (CABG) surgery were equally stratified into 3 series of 60 patients with the routinely used oxygenators; Capiox RX-25, CML Duo and Quadrox-D. Then they were randomised by drawing lots and allocated into the LMSRL or GPE groups. We compared hematocrit, hemoglobin, platelet count, activated clotting time (ACT), lactate and colloid osmotic pressure (COP), blood loss, transfusion need, urine production and ICU stay. In addition, we monitored the average trans-oxygenator fluid resistance (AFR) for each type of oxygenator. RESULTS: The COP is significantly lower in the LMSRL group (20mmHg +/- 0.2 versus 18 mmHg +/- 0.2, p < 0.0001); as was the total use of plasma expanders (3846 ml +/- 98 versus 3059 ml +/- 77, p < 0.001). All other parameters were not significantly different. When comparing the observed AFR for the three types of oxygenators, a lower AFR in the LMSRL group (p < 0.02) was noted for the Capiox RX-25. CONCLUSIONS: This study shows a lower need for plasma expanders in patients who receive only starch plasma expanders. Further, we noted a lower COP in the LMSRL group, but since the mean COP was >17 +/- 0.2 mmHg, this cannot be considered of clinical importance. In conclusion, our study result supports the use of low molecular starch as a good alternative choice for priming CPB.

Prospective double-blind randomized study of the effects of four intravenous fluids on platelet function and hemostasis in elective hip surgery.

A prospective randomized double-blind study was performed to determine the effects of three colloids, Haemaccel, Gelofusine and albumin, and also saline on platelet activation, platelet aggregation (induced by adenosine diphosphate (ADP), epinephrine, collagen) platelet agglutination by ristocetin and other hemostatic variables in 55 patients undergoing primary unilateral total hip replacement. The fluids were administered according to normal clinical practice and assessments were made immediately before, at the end, and 2 h after the end of surgery. Surgery was accompanied by thrombin generation (increases in thrombin/antithrombin III complex, prothrombin F1 +2 fragment) platelet activation (betaTG) and compromised coagulation. Generally, the platelet activation appeared to result in platelet desensitization and brought about a persistent reduction in platelet aggregation to ADP and epinephrine, irrespective of the fluid used. Additionally, Haemaccel and Gelofusine inhibited ristocetin-induced platelet agglutination and albumin inhibited collagen-induced platelet aggregation. Gross inhibitory effects of Haemaccel that had been predicted from an earlier in vitro study did not occur. Particular fluids had selective additional effects on the hemostatic system. Albumin infusion served to maintain plasma albumin at normal concentrations postsurgery. The two gelatin preparations, Haemaccel and Gelofusine, maintained plasma viscosity. All three colloids led to a transient increase in activated partial thromboplastin time postsurgery and also a transient fall in the concentration of factor VIII, which were accompanied by a transient increase in bleeding time, but there was no measurable increase in blood loss. Inhibition of platelet aggregation by certain colloids may provide additional protection against the increased thrombotic risk in patients following major surgery.

[Acute normovolaemic haemodilution in children]. / Sródoperacyjna normowolemiczna hemodylucja u dzieci.

Acute normovolemic haemodilution was performed in 34 children (4-6 years old, weight: 16-68 kg) in whom major blood loss was expected during operation. Anaesthesia was induced with thiopentone, and then maintained with N2O/O2, fentanyl and pipecuronium. IPPV was used to maintain normocapnia. Heart rate, blood pressure, central venous pressure and core body temperature were monitored during haemodilution and throughout the surgery. A predetermined volume of blood to reduce hematocrit value to 30% was withdrawn in standard collection bags. In one child from Jehovah's Witness family hematocrit following haemodilution was only 20%. Every 1 ml of withdrawn blood was replaced with 1 ml of Haemaccel (Boehring, 32 children) or with 3 ml of isotonic crystalloid solution (PWE Polfa, 2 children). The blood lost during surgery was replaced with crystalloid solution and Haemaccel. Normovolemic loss of blood to haematocrit value of 20-24% was permitted. Retransfusion of collected blood was started when major bleeding was over, or when hematocrit decreased below 20-24%. Only 8 children needed homologous blood transfusion. Heart rate decreased significantly during haemodilution, while blood pressure remained stable. Low initial haematocrit and coagulopathy due to dilution of the plasma clotting factors were the limiting factors of the method. Partial thromboplastin time and plasma fibrinogen should be monitored throughout surgery, because the occurrence of coagulopathy promptly allows to initiate retransfusion of autologous blood.

A prospective randomized study comparing two techniques of perioperative blood conservation: isovolemic hemodilution and hypervolemic hemodilution.

UNLABELLED: We compared hypervolemic hemodilution (HVH) and isovolemic hemodilution (IVH) as means of perioperative blood conservation under standardized conditions. Thirty ASA status I/II adults slated for orthopedic, ear-nose-throat, or general surgery with expected blood loss of >500 mL underwent either IVH (n = 15) or HVH (n = 15). They were hemodiluted to a hematocrit (Hct) of 25% by blood withdrawal and simultaneous polygeline (Hemaccel((R))) infusion (IVH) or by infusing polygeline without blood withdrawal, thus creating hypervolemia (HVH). Further blood loss to a Hct of 20% was allowed before autologous/allogeneic blood transfusion to aim for a 24-h postoperative Hct of > or =25%. Systolic blood pressure (P = 0.0107) and central venous pressure (P = 0.0281) were significantly higher during HVH. The mean difference (MD) between the target postdilution Hct of 25% and the Hct achieved was not statistically significant in either group (MD [95% confidence interval; CI], 0% [-0.7% to 0.7%] for IVH and 0.6% [-0.1% to 1.3%] for HVH). The actual amount of allogeneic blood used was similar in the two groups, with an MD (95% CI) of -7 (-326 to 312), and was significantly less than the corresponding projected amount (MD [95% CI], -581 mL [-753 to -409 mL] in IVH; -376 mL [-531 to -221] in HVH). The two techniques were similar in time taken (MD [95% CI] = 7 min [-0.5 to 14.5 min]), cost incurred (MD [95% CI] = $1.7 (-$4.10 to $7.50]), and volumes of polygeline used (MD [95% CI] = -6 mL/kg body weight [-16 to 4 mL/kg body weight]). This study found IVH and HVH comparable in significantly reducing perioperative allogeneic blood requirements, time needed, and cost incurred. The formula used for achieving the desired HVH appears promising. IMPLICATIONS: Both hypervolemic hemodilution (HVH) and isovolemic hemodilution (IVH) claim to reduce red blood cell loss during surgery by diluting the patient's blood. This study found both comparable in significantly reducing the exposure to bank blood in the perioperative period, the time needed, and the cost incurred. HVH, being simpler, because it does not involve blood withdrawal, appeared superior to IVH in the healthy adults studied. Larger studies are needed to substantiate the results.

Corpus cavernosum as an alternative means of intravenous access in the emergency setting.

BACKGROUND: The present study was designed to investigate the feasibility of using the corpus cavernosum as an alternative means of intravenous access in the emergency setting. METHODS: The feasibility of achieving the infusion flow rates was first ascertained using direct intracavernous infusion of normal saline. The effect of atropine and adrenaline when given via this route was then studied. Hypovolaemic shock was then induced in dogs who were then actively resuscitated via this route using normal saline, Haemaccel and whole blood. RESULTS: Infusion flow rates were achieved for normal saline of 32.3, 50.3 and 67.3 mL per min at 100, 200 and 300 mmHg pressure, respectively. The peak effects of atropine and adrenaline via this route were seen at approximately 1 min after injection. Resuscitation using this method was uniformly successful in all dogs via the corpus cavernosum, with all reaching or exceeding their premorbid central venous pressure (CVP), and approaching or reaching their premorbid mean arterial pressure (MAP). In comparison the control dog's CVP and MAP did not rise during the period of observation after it was bled. CONCLUSIONS: The corpus cavernosum is a practical alternative means of intravenous access in the emergency setting in the dog model.

Microparticle-containing oncotic solutions augment in-vitro clot disruption by ultrasound.

Echocardiographic contrast agents enhance blood clot disruption by ultrasound. It has been suggested that the microbubbles add nuclei for the enhancement of cavitation by ultrasound. However, microbubbles are rapidly destroyed by the ultrasound energy. We assessed whether non-gas filled colloidal solutions (hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides) will facilitate clot disruption by ultrasound. In two separate experiments human blood clots, 200-400 mg in weight, were weighed and then immersed for 15 seconds in 10 ml normal saline solution containing 0%, 0.1%, 1%, 2%, and 5% of hyperoncotic medium molecular hydroxyethyl starch or 0%, 0.035%, 0.175%, 0.35%, and 0.7% degraded gelatin polypeptides. Clots were randomized to 10 seconds 20 kHz ultrasound or immersion without ultrasound. After treatment, the clots were reweighed, and the percent difference in weight was calculated. Non-gas filled microparticle-containing solutions such as hyperoncotic medium molecular hydroxyethyl starch and degraded gelatin polypeptides significantly augmented blood clot disruption by ultrasound. The effect is dependent on the colloidal solution concentration with maximal effect achieved with 1% hyperoncotic medium molecular hydroxyethyl starch and 0.35% degraded gelatin polypeptides.

[The effects of moderate acute normovolemic hemodilution on intestinal oxygen supply and consumption in anesthetized cats].

OBJECTIVE: To study the effects of moderate acute normovolemic hemodilution on the intestinal blood perfusion and oxygen supply in cats. METHODS: 15 domestic male cats were hemodiluted with Haemaccel. HR, MAP, lactate concentration in superior mesenteric vein (LAC), superior mesenteric artery blood flow (SMABF), superior mesenteric artery and venous blood gas analysis were recorded and the intestinal oxygen delivery (DO(2)), oxygen consumption (VO(2)) and oxygen extraction (EO(2)) were calculated before and after hemodilution. RESULTS: SMABF increased obviously (P < 0.05), intestinal DO(2) and EO(2) did not change (P > 0.05) but VO(2) increased (P < 0.05), and LAC in superior mesenteric vein did not increase. CONCLUSIONS: Moderate acute normovolemic hemodilution with Haemaccel do not alter intestinal oxygen delivery by increasing the superior mesenteric blood flow. It means that intestinal mucosa ischemia does not happen during moderate acute normovolemic hemodilution.

Cardiopulmonary effects of 7.2% saline solution compared with gelatin infusion in the early postoperative period after coronary artery bypass grafting.

OBJECTIVE: We report a clinical study on the use of 7.2%, 2400 mOsm/L, hypertonic saline solution compared with gelatin in early postoperative period after coronary artery bypass surgery. METHODS: Two groups (n = 10 each) received 5 ml/kg of either saline solution or gelatin over 1 hour. Cardiac index, central venous pressure, pulmonary capillary wedge pressure, systemic and pulmonary vascular resistance indices, arterial oxygen tension, plasma osmolarity, electrolytes, and urinary output were recorded before starting the infusion and subsequently at 10, 30, 60, 90, 120, 240 and 600 minutes. Plasma creatinine, urea, electrolytes, urinary volume, and sodium excretion were measured at 12 and 24 hours. RESULTS: There were no significant demographic or operative difference between the groups. Patients receiving saline solution had a larger diuresis at 12 (p = 0.0008) and 24 hours (p = 0.002), with less positive balance at 12 hours (p = 0.0008). The group receiving saline solution had better cardiorespiratory recovery with shorter extubation time (p = 0.033), and earlier increase in cardiac index with a positive correlation between plasma sodium content and cardiac index. Maximum increase in cardiac index (+31%) occurred at 60 minutes (p = 0.025) associated with 8% increase in plasma sodium content (r = 0.51, p = 0.01), without a concomitant rise in pulmonary capillary wedge pressure. The group receiving gelatin had a linear increase in cardiac index with increasing pulmonary capillary wedge pressure, reaching +16% from baseline by 90 minutes. Compared with the gelatin-treated group, patients receiving saline solution had unchanged systemic vascular resistance index but a significantly lower pulmonary vascular resistance index with a negative correlation to plasma sodium content. There was no difference in levels of urea and creatinine. No side-effect attributable to the use of saline solution was observed.

Influence of fluid resuscitation on renal function in bacteremic and endotoxemic rats.

PURPOSE: Fluid resuscitation, which is the most important primary therapy in sepsis, is not always able to prevent acute renal failure. In this study, we investigated in two different rat models of distributive shock whether fluid resuscitation would increase renal plasma flow (RPF) and subsequently glomerular filtration rate (GFR). MATERIALS AND METHODS: In pentobarbital anesthetized wistar rats Haemaccel (Behring Pharma, Hoechst, the Netherlands) infusion (1.2 mL/100 g/h for 3 hours) was started immediately during either bacteremia (bolus of living Escherichia coli bacteria, 10(9) or endotoxemia (1 hour infusion of E. coli endotoxin, 8 mg/kg), as well as in time-matched healthy controls. RESULTS: After 3 hours, this treatment had increased RPF (clearance of 131I-hippurate) above normal in control (+67%) and bacteremic rats (+75%), whereas in endotoxemic animals, the significantly decreased RPF was normalized. On the other hand, in bacteremic animals, the lowered GFR (clearance of creatinine; x44%) was normalized, whereas in endotoxemic animals GFR remained depressed (x30%). The lack of improvement in GFR during endotoxemia was also indicated by a profound fall in urine flow, which by contrast steadily increased in control and bacteremic rats owing to volume loading. In both shocked groups, the decreased renal oxygen delivery was normalized, but the higher renal oxygen consumption than expected on the basis of the work needed for sodium reabsorption was not influenced by Haemaccel treatment, despite the fact that it caused this work load to rise in bacteremic but not in endotoxemic rats. In both shock models, renal cortical adenosine triphosphate content did not differ from healthy controls and was not influenced by volume loading. CONCLUSIONS: In conclusion, our study suggests that a decrease in GFR caused by live bacteria in the circulation may benefit from fluid resuscitation, while during endotoxemia this therapy could not prevent acute renal failure.

Seguridad del Haemaccel/Solucel en pacientes sometidos a hemodilución normovolémica intencional preoperatoria (Estudio multicéntrico internacional)

El uso de Haemaccel/Soluccel en 305 pacientes sometidos a hemodilución preoperatoria normovolémica intencional, ha sido documentada en un estudio abierto, prospectivo, multicéntrico, controlado y multinacional (doce centros en 5 países). Los hallazgos reproducen el índice bajo de efectos adversos encontrados en la literatura corriente

Fluid therapy with Ringer's solution versus Haemaccel following coronary artery bypass surgery.

BACKGROUND: Crystalloid and colloid infusion can be used in volume therapy following heart surgery. In this prospective, randomised study we compared Ringer's solution (group R) to Haemaccel (group H) following coronary artery bypass grafting. METHODS: A stringent protocol for adjusting the infusion rate was used. Haemodynamic parameters and pulmonary function were evaluated as well as chest tube drainage. The double-indicator dilution method was used to measure total blood volume index (TBVI), intrathoracic blood volume index (ITB-VI) and extravascular lung water index (EVLWI). RESULTS: Haemodynamic stability was achieved in both groups throughout the study period, as judged from mean arterial pressure, central venous pressure, pulmonary capillary wedge pressure, and cardiac index. However, the total volume infused was significantly higher in group R. TBVI and ITBV were higher in group H, although only significant at 8 h for TBVI. Pulmonary function was similar in both groups. There was no significant difference in EVLWI, pulmonary shunt fraction, and time on mechanical ventilation. Likewise, chest tube drainage was not significantly different in both groups. CONCLUSION: We conclude that volume therapy with Haemaccel following heart surgery requires less volume and achieves better filling of the circulation compared to Ringer's solution.

A comparison of 4.5% human albumin solution and Haemaccel in neonates undergoing major surgery.

In a randomized blinded study we compared two colloid solutions in 30 neonates undergoing major surgery. Fifteen neonates received 4.5% Human albumin solution (HAS) (mean volume 25.6 ml.kg-1, SD 9.5) and the others received Haemaccel (Hoechst) (24.9 ml.kg-1, SD 10). Pre and postoperative plasma albumin and haemoglobin concentrations and plasma colloid osmotic pressure (COP) were compared. In the group given Haemaccel there was an appreciable and statistically significant decrease in the mean plasma albumin concentration from 34.27 to 28.27 g.1(-1) (mean difference 6, CI 3.38 to 8.62) and the mean COP decreased significantly from 22.2 to 19.9 mmHg (mean difference 2.3, CI 0.3 to 4.5). In the HAS group there was no significant change in either the plasma albumin concentration or COP. There was a small but significant decrease in the mean haemoglobin concentration from 15.92 to 14.35 g.dl-1 (mean difference 1.56, CI 0.57 to 2.55) after HAS. We conclude that HAS is the superior colloid for volume replacement in neonates undergoing surgery.

A comparison of albumin, polygeline and crystalloid priming solutions for cardiopulmonary bypass in patients having coronary artery bypass graft surgery.

This study was designed to assess the effect of different prime solution compositions on a patient's fluid balance, transfusion requirements, renal function and haemodynamic stability over the first 24 hours postbypass. Ninety-three patients presenting for first-time coronary artery bypass graft (CABG) surgery were randomly allocated to receive one of three prime solutions for the CPB pump: albumin (4.6%) + Plasmalyte (Group A, n = 32), polygeline (Hemaccel) + Plasmalyte (Group P, n = 29), or crystalloid (Plasmalyte) alone (Group C, n = 32). Patients, anaesthetists, surgeons and intensive care unit (ICU) staff were all blinded as to the solution type. The groups were demographically and haemodynamically similar. There were no differences between the groups with respect to white cell or platelet counts during the study. There was a significant difference in haemoglobin levels between the groups on weaning from CPB and on arrival in the ICU (Group C > Groups P and A, p < 0.001 for both times). There was no difference in blood transfusion requirements between any of the groups. During CPB, Group C required significantly more crystalloid than the other groups (p < 0.001). Urine output was significantly higher in Group C compared with Groups P and A at all time periods up to and including ICU 12 hours (p < 0.05). The use of frusemide was significantly higher in the ICU in Groups P and A (p < 0.01). There was a net gain of 3132 +/- 412 ml in Group C in 24 hour fluid balance, which was significantly higher than Group A (2166 +/- 223 ml, p = 0.04). Our results show that, in this patient population, there is no advantage in using a colloid-based prime solution over a purely crystalloid solution from a haemotologic or haemodynamic point of view for the first 24 hours after CPB. There appears to be an increase in extracellular fluid (ECF) retention in Group C, but this caused no related problems in the study period. On the other hand, diuretics (frusemide) needed to be given significantly less often in these patients to offset oliguria.

Haemodynamic effects of subarachnoid block in elderly patients.

We have studied the haemodynamic effects of subarachnoid block in elderly patients. Thirty patients were undergoing elective transurethral surgery and 18 non-elective orthopaedic surgery, predominantly fractured neck of femur. Systolic arterial pressure (SAP) was measured by automated oscillotonometry, central venous pressure (CVP) by manometer and cardiac index (CI), stroke index (SI) and heart rate (HR) by transthoracic electrical bioimpedance. Systemic vascular resistance index (SVRI) was derived. SAP decreased by more than 25% in 33 patients and SVRI showed similar decreases (P = 0.0001). CVP decreased (2.5 (SD 1.5) cm H2O) in all patients. CI was unaffected because a decrease in SI in some patients (13 (19)%; P = 0.01) was compensated for by an increase in HR (13 (13)%; P = 0.01). Decreases in SAP of 25% were treated initially with colloid solution 8 ml kg-1, which restored SAP in 19 patients. CVP, SI and HR were all restored to baseline values, however, SVRI was decreased further (P < 0.05). Fourteen patients required additional treatment with metaraminol which restored SVRI to baseline values. Patients with systolic hypertension were more likely to require treatment with metaraminol (P = 0.04).

Incidence and clinical importance of perioperative histamine release: randomised study of volume loading and antihistamines after induction of anaesthesia. Trial Group Mainz/Marburg.

Although histamine release is recognised as a common event during anaesthesia and surgery, few clinicians judge the resultant cardiorespiratory disturbances serious enough to warrant prophylaxis with antihistamines. We have assessed the incidence and importance of histamine release in a randomised 2 x 2 factorial study. 240 patients representing a routine throughput of major general surgery were studied during a standardised induction of anaesthesia and preoperative loading of the circulation with either Ringer solution or Haemaccel-35, with or without antihistamine prophylaxis with dimetindene (H1) plus cimetidine (H2). Cardiorespiratory disturbances were graded as detectable, clinically relevant, or life-threatening from observers' records of the anaesthesia and the actions taken by the anaesthetists. Disturbances that were accompanied by significant rises in plasma histamine were further designated histamine-related, and those that were not were designated histamine-unrelated. Anaesthetists, observers, and designators were blinded to whether or not the patients had received antihistamines and to which solution was used for circulatory volume loading. Clinically relevant or life-threatening histamine-related disturbances occurred in 8% of the patients who after induction of anaesthesia received Ringer without antihistamines, in 26% of those who received Haemaccel without antihistamines, and in 2% or less of those who received antihistamines (p < or = 0.0001). There were 4 life-threatening histamine-related disturbances, all in patients who received Haemaccel without antihistamines (p < 0.01). Histamine-unrelated disturbances occurred in 16% overall, with no obvious effect of Haemaccel or antihistamines. The histamine-related disturbances under anaesthesia were remarkable for their severity (even with small rises in histamine concentrations), for the prevalence of bradycardia, and for the absence of skin signs. Their likelihood and severity were increased in patients with tumours. The results of the trial make a case for routine prophylaxis with antihistamines as part of anaesthetic management.