K. Messmer

Acceptable hematocrit levels in surgical patients

The ready availability of blood and blood components has resulted in a liberal use of blood transfusions; however, the transfusion of blood is still associated with significant risks for the recipient. The appearance of the acquired immunodeficiency syndrome and the evidence that homologous blood can induce immunosuppression and thereby impair the host resistance of surgical patients has led to a reconsideration of the indications for blood transfusions. It has also fostered application of alternative methods with the aim of reducing the number of homologous blood transfusions. Based on the data available from studies on intentional perioperative hemodilution in patients undergoing elective surgery, and data from patients in intensive care, a hematocrit level of about 30% is acceptable for surgical patients, provided oxygen transport is not impaired by the reduced saturation of arterial blood or inadequate perfusion. The basic mechanism that compensates for the reduced oxygen capacity of the blood is a rise in cardiac output and stroke volume, both depending on adequate venous return and myocardial function. The hematocrit setpoint has to be determined for the individual patient with regard to the history of the underlying disease, circulating blood volume, and actual oxygen needs. By accepting a perioperative hematocrit level of 30% for patients without respiratory and cardiac disease or increased oxygen demand, respectively, the number of transfusions of homologous blood can be reduced and dangerous side effects can be avoided.RésuméLa grande facilité à disposer de sang ou de constituants a abouti à lemploi excessif des transfusions sanguines. Dautre part la transfusion de sang présente toujours des risques pour le receveur. Lapparition du SIDA et le fait indiscuté que le sang homologue peut induire une immunosuppression préjudiciable à la résistance des malades chirurgicaux ont conduit à reconsidérer les indications de la transfusion de sang et à favoriser lemploi dautres méthodes dont le but est de réduire le nombre des transfusions de sang homologue. En se référant aux données fournies par les études de lhémodilution péri-opératoire intentionnelle dans la chirurgie élective et aux données fournies par les malades traités par soins intensifs, il a été établi quun hématocrit aux environs de 30% est acceptable chez les malades chirurgicaux dés lors que le transport de loxygène nest pas altéré par une réduction de la saturation du sang artériel ou par une perfusion inadéquate. Le mécanisme de base qui intervient pour compenser la réduction de loxygénation du sang consiste en une élévation du débit cardiaque et du sang éjecté, ces deux facteurs dépendant dun retour veineux et dune fonction myocardique adéquats. Le point de lhematocrit à prendre en considération doit être déterminé pour chaque malade en fonction de la maladie quil présente, du volume de sang circulant, et des besoins réels en oxygène. En fixant ce point à 30% chez les patients qui ne présentent pas daffections cardiaque ou respiratoire ou encore une augmentation de la demande en oxygène, il est possible de réduire le nombre de transfusions de sang homologue et déviter les effects secondaires indésirables de la transfusion.ResumenLa fácil disponibilidad de sangre y de componentes sanguíneos ha resultado en la liberación en el uso de transfusiones. Sin embargo, la transfusión de sangre todavía se halla asociada con riesgos de significación por parte del recipiente. La aparición del SIDA y la evidencia de que la sangre homóloga puede inducir inmunosupresíon y con ello alterar los factores de resistencia de huésped en los pacientes quirúrgicos, ha llevado a reconsiderar las indicaciones para transfusion sanguínea y ha promovido la aplicación de métodos alternativos de autotransfusión con el propósito de reducir el número de transfusiones homólogas. Con base en la información disponible derivada de estudios con hemodilución perioperatoria intencional en cirugía electiva y de pacientes en cuidado intensivo se considera que un hematocrito de 30% es aceptable en pacientes quirúrgicos, siempre y cuando el transporte del oxǵeno no se encuentre alterado por una saturación reducida de la sangre arterial o por perfusión inadecuada. El mecanismo basico de compensación ante una reducida capacidad de oxigenación de la sangre es el aumento en el gas to cardíaco y en el volumen de eyección, factores que a su vez dependen de adecuado retorno venoso y de buena función miocárdica. El nivel crítico del hematocrito debe ser establecido para cada paciente individual en relación a la historia de la enfermedad actual, del volumen circulatorio, y de las demandas reales de oxígeno. Al aceptar un hematocrito preoperatorio de 30% para pacientes libres de enfermedad respiratoria y cardíaca o de demanda aumentada de oxígeno, se puede lograr la reducción en el número de transfusiones de sangre homóloga y evitar los peligrosos efectos colaterales.

The hairless mouse ear for in vivo studies of skin microcirculation

The homozygous (hr/hr) hairless mouse ear was introduced in 1980 by Eriksson and coworkers as a model for in vivo studies of the skin microcirculation. Herein we expand on this work, presenting results of in vivo microvascular parameter measurements and morphologic studies in the intact ear. The in vivo measurements include microvascular diameter, RBC velocity, capillary density, and the frequency and amplitude of arteriolar vasomotion. In connection with the in vivo studies, a detailed anatomic description of the overall and vascular anatomy is given. Additionally, the preparation techniques for carrying out these in vivo and morphologic studies in the mouse ear are presented in detail.

Instantaneous restoration of regional organ blood flow after severe hemorrhage: effect of small-volume resuscitation with hypertonic-hyperoncotic solutions.

The acute effects of small-volume infusion of hypertonic-hyperoncotic solutions on central hemodynamics, regional organ blood flow (RBF; 15-microns-diameter radiolabeled microspheres), and respiratory function following severe hemorrhage (MAP = 40 mm Hg for 45 min, approx 50% blood loss) were analyzed in anesthetized beagles. Treatment regimens used were: 10% Dextran 60 in 7.2% NaCl (HHS); 10% Dextran 60 in 0.9% NaCl (HDS); or 7.2% NaCl (HSS) alone, administered over 2 min in a volume equivalent to 10% of the blood loss (4 ml/kg iv). Within 5 min, cardiac output reached (HSS, HDS) or even exceeded prehemorrhage values (HHS), and MAP increased to 56% (HDS)-74% (HHS) of baseline. At the same time, RBF in kidneys (all groups), pancreas (HHS, HSS) and gastric mucosa (HHS) was completely restored, while flow in myocardium, brain, skeletal muscle, adrenal glands (all groups), and small intestine and colon (HHS) rose even above baseline values (P less than 0.05). Fractional blood flow (percentage of cardiac output) favored heart and brain in all three groups. These effects tended to persist for at least 30 min. Respiratory function was not affected by either of the three solutions, and no adverse effects were noted. Small-volume resuscitation with 7.2% saline/10% Dextran 60 provides instantaneous restitution of regional organ blood flow; it appears to result in a more uniform circulatory response than 7.2% saline or 10% Dextran 60 alone and might ensure improved organ perfusion during evacuation of patients from the accident site.

Hemodilution ‐ possibilities and safety aspects

Normovolemic hemodilution is an essential part of the overall strategy to avoid exposure of patients to the hazards of homologous blood transfusions. It includes beneficial effects on the flow properties and flow conditions of blood. A hematocrit of 30% can be regarded as an optimal compromise between the fluidity and the oxygen content of the blood. Compensatory responses such as increased cardiac output and stroke volume occur following hemodilution. In patients with compromised coronary reserve the degree of hemodilution that is tolerated has to be carefully considered. Therefore specific selection criteria for patients to be preoperatively hemodiluted are needed. For reasons of safety, efficiency and practicability colloid solutions rather than crystalloid solutions should be used for intentional hemodilution.

The use of plasma substitutes with special attention to their side effects

Plasma protein fraction and human serum albumin are suitable for plasma replacement; however, they are in short supply and extremely expensive. Fresh-frozen plasma should not be used for volume replacement, but for documented coagulation protein deficiencies and for patients who require massive blood transfusions. Artificial colloids are free from the risk of transmitting diseases and easy to provide at low costs. The intravascular volume effect of colloid solutions based on dextran, gelatin, or hydroxyethyl starch depends on the physicochemical characteristics of the polymer solution. For the given colloid, the half-life varies from 2 to 8 hours. In addition to the volume effect, dextran provides specific antithrombotic properties. None of the colloids are free from the risk of untoward effects, such as anaphylactoid/anaphylactic reactions. The low frequency of these reactions and the possibility to prevent and to treat them justifies the use of artificial colloids on a routine basis for shock treatment, volume support, and perioperative hemodilution.RésuméLa fraction protéique plasmatique et la sérum-albumine sont capables dassurer le remplacement du plasma mais elles sont peu abondantes et très coûteuses. Le plasma frais congelé ne doit pas être employé pour rétablir la volémie mais seulement pour corriger les déficiences protéiques de la coagulation et pour traiter les sujets qui ont besoin de transfusions massives de sang. Les solucións colloïdes artificielles évitent le risque de transmission des maladies et sont peu onéreuses. Leffet volémique intravasculaire des solutions colloïdales à base de dextran, gélatine ou amylopectine dépend des caractères physico-chimiques de la solution polymère. Leur demi-vie varie de 2 à 8 heures. En plus de son effet volumétrique, le dextran possède des propriétés antithrombotiques spécifiques. Aucune des solutions colloïdales nest exempte du risque deffets indésirables, par exemple des réactions anaphylactiques ou anaphylactoïdes. La fréquence réduite de ces réactions et la possibilité de les prévenir ou de les traiter, justifient lemploi étendu des solutions colloïdales artificielles pour compenser le choc hypovolémique et lhémodilution.ResumenLa fractión proteica del plasma y la albúmina sérica humana son sustitutos adecuados del plasma; sinembargo, estos materiales son escasos y extremadamente costosos. El plasma fresco congelado no debe ser utilizado para reemplazo de volumen circulatorio, según la conclusión de una reciente Conferencia de Consenso del Instituto Nacional de Salud de E.U.A., y su uso sólo está indicado en casos de deficiencias documentadas de factores proteicos de coagulatión y en pacientes que requieren transfusiones masivas. Los coloides artificiales son sustancias libres del riesgo de transmisión de enfermedades y de fácil consecusión a bajos costos. El efecto sobre el volumen intravascular de las soluciones coloides a base de dextrán, gelatina o almidón hidroxietílico depende de las características fisicoquímicas de la solución polímera, y su vida media oscila entre 2 y 8 horas. Además de su efecto sobre el volumen circulatorio, el dextrán posee propiedades antitrombóticas específicas. Ninguno de los coloides se halla libre de efectos colaterales indeseables, especialmente de reacciones anafilactoides/anafilácticas. La baja tasa de incidencia de tales reacciones y la buena posibilidad de su prevención y tratamiento, justifica el uso de los coloides del volumen circulatorio en el shock y para efectos de hemodilución perioperatoria.

Direct monitoring of nutritive blood flow in a failing skin flap: the hairless mouse ear skin-flap model.

A new experimental skin-flap model is presented in which direct observations of blood flow in individual capillaries can be made from the time of flap creation throughout the entire evolution of the establishment of necrosis. After flap creation, one observes through the microscope that at 1 hour a large area of tissue is nonperfused as a result of the surgical trauma. This is followed by vasodilatation at 6 hours, resulting in an increase in the area of perfused tissue. At 24 hours, the vasodilatation persists, and the red cells that have entered the tissue during the vasodilatation (6 hours) accumulate in the capillaries, this being reflected by an increased area of nonperfused tissue. This increase continues to 72 hours, at which time the perfusion-nonperfusion interface becomes well defined and remains so throughout the 5-day experiment. Analyses of the relationship between early postoperative capillary perfusion and eventual necrosis are presented. Advantages and disadvantages of this model are listed.

Quantitative analysis of neovascularization of different PTFE-implants

The process of neovascularization was analyzed in vivo in different expanded polytetrafluoroethylene (e-PTFE) implants which are frequently used in cardio-thoracic and vascular surgery. We have used the model of the hamster dorsal skinfold chamber which allows quantitative analysis of the microcirculation by means of intravital fluorescence microscopy. Pieces of approximately 1 mm2 of the cardiovascular patch (CVP, fibril length: 30 microns; n = 21), surgical membrane (SM, fibril length: 1 micron; n = 16), and soft tissue patch (STP, fibril length: 22 microns; n = 12) were implanted into the skinfold chambers. On day 10 after implantation, the functional density of newly formed microvessels was significantly (P less than 0.05) higher in CVP (145.0 +/- 10.9 cm-1) as compared to SM (688 +/- 13.9 cm-1) and STP (86.9 +/- 21.2 cm-1). In addition, CVP revealed a larger zone of neovascularization (311.6 +/- 19.4 microns) and the tightest integration (dynamic breaking strength: 17.9 +/- 3.0 cN/mm2) into the perigraft tissue, while SM demonstrated only few microvessels and no integration (6.0 +/- 1.9 cN/mm2) into the perigraft. None of the three different PTFE-implants revealed transmural ingrowth of capillaries. The internodal distance of PTFE implants seems to be the most important factor for neovascularization. Surgical membrane used for the replacement of passive biological membranes demonstrated, as is its purpose, little neovascularization and no integration into the perigraft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Improvement of skin flap perfusion by subdermal injection of recombinant human basic fibroblast growth factor.

The effect of subcutaneously injected recombinant human basic fibroblast growth factor (bFGF) was studied in an arterial skin flap model on the ear of the hairless mouse. Fifty-three male, hairless mice were randomly assigned to 4 groups and pretreated in two different time intervals with different doses of human bFGF. Microvascular perfusion of the skin flaps was determined over a 5-day period by means of intravital microscopy after intravenous injection of the fluorescence marker fluorescein isothiocyanate—dextran (M, 150,000). Human bFGF (2,700 ng) injected 6 days before flap creation could not improve perfusion of the flap (n = 10) when compared with controls. However, when applied 18 days before flap creation (n = 13), the same dose resulted in a significant reduction of nonperfused tissue at day 5 after flap creation (12.3% vs 26.8%, p < 0.01). Eighteen-day pretreatment with 1,200 ng (n = 10) and 480 ng (n = 10) had no significant effect on skin flap perfusion. We conclude, therefore, that successful pretreatment with bFGF for prevention of skin flap necrosis is time and dose dependent.

MIC-III — an integrated software package to support experiments using the radioactive microsphere technique

MIC-III is a versatile program system to support gamma spectrometry data management and data collection for experiments using the radioactive microsphere technique. It is mainly written in PASCAL and running on a minicomputer. Hierarchical organ dissection schemes are used for unique classification and identification of samples. For each series of experiments, up to 12 different nuclides and up to 20 different organ dissection schemes can be handled simultaneously. Sample weights are collected on-line and sample radioactivities are measured automatically by gamma spectrometry under process control. The spectra with a resolution of 1022 channels are analyzed using a modified linear regression technique and a strategy to compensate for global spectrum shifts. The spectrum deconvolution algorithm was evaluated by calculating the recovery indices for known nuclide mixtures and compared to the stripping method, matrix method and a linear regression technique using window counts. Recovery values produced by MIC-III are better balanced than those of the other methods. MIC-III showed the smallest dispersion of the recovery index and exhibited least error accumulation in case of spectrum shift. MIC-III computes regional blood flow and arterio-venous shunt, and provides interfaces to customized programs or statistical software packages for further analysis. It has successfully been employed in more than 140 experiments.

White cell-endothelium interaction during postischemic reperfusion of skin and skeletal muscle.

Reperfusion failure after prolonged ischemia is characterized by sequestration of granulocytes within the microvasculature of the ischemic organs and tissues. Leukocytes, activated by tissue trauma, complement factor C5 and/or endotoxin interact with the endothelium surface and eventually emigrate through the vessel wall into the perivascular tissue. Sticking and emigration of polymorphonuclear granulocytes (PMN) is associated with formation of oxygen derived radicals and leakage of plasma through the microvascular walls indicating disturbance of the endothelial barrier function.1,2