Kai Heckel

Perioperative fluid and volume management: physiological basis, tools and strategies

Fluid and volume therapy is an important cornerstone of treating critically ill patients in the intensive care unit and in the operating room. New findings concerning the vascular barrier, its physiological functions, and its role regarding vascular leakage have lead to a new view of fluid and volume administration. Avoiding hypervolemia, as well as hypovolemia, plays a pivotal role when treating patients both perioperatively and in the intensive care unit. The various studies comparing restrictive vs. liberal fluid and volume management are not directly comparable, do not differ (in most instances) between colloid and crystalloid administration, and mostly do not refer to the vascular barriers physiologic basis. In addition, very few studies have analyzed the use of advanced hemodynamic monitoring for volume management.This article summarizes the current literature on the relevant physiology of the endothelial surface layer, discusses fluid shifting, reviews available research on fluid management strategies and the commonly used fluids, and identifies suitable variables for hemodynamic monitoring and their goal-directed use.

Role of PARP on iNOS pathway during endotoxin-induced acute lung injury

Objective Excessive nitric oxide (NO) and especially peroxynitrite may cause pulmonary tissue damage, e.g., through lipid peroxidation and/or exhaustion of cellular energy depletion induced by activation of poly (ADP-ribose) polymerase (PARP). Furthermore, PARP seems to aggravate tissue destruction by regulating the expression of respective genes.Design Prospective animal study.Setting University research laboratory.Intervention We investigated the effect of competitive PARP inhibition by 3-aminobenzamide (3-AB) on the pulmonary iNOS pathway after infusion of lipopolysaccharide (LPS).Measurements and results The pretreatment of rabbits with 3-AB attenuated the LPS-induced iNOS mRNA and protein expression analyzed by RT-PCR and Western blot, and plasma nitrite concentrations quantified by Griess reaction (71±6%, 93±6% vs baseline). Electromobility shift assay showed an enhanced NF-κB and attenuated AP-1 activation after 3-AB vs LPS alone. Lipid peroxidation determined as levels of thiobarbituric acid reactive substances in plasma and lung tissue was reduced by 50% in the LPS+3-AB in comparison to LPS alone. Simultaneously, 3-AB was able to inhibit correspondingly the LPS-induced extravasation of gold-labeled albumin and increase of alveolo-arterial oxygen difference.Conclusion PARP regulates the pulmonary NO pathway during endotoxemia via AP-1 and not NF-κB. Thus, pharmacological inhibition of PARP might be an effective intervention to prevent endotoxin-induced lung injury, interrupting the vicious circle of NO production and PARP activation.

Hemodynamic management of septic shock: is it time for "individualized goal-directed hemodynamic therapy" and for specifically targeting the microcirculation?

ABSTRACT Septic shock is a life-threatening condition in both critically ill medical patients and surgical patients during the perioperative phase. In septic shock, specific alterations in global cardiovascular dynamics (i.e., the macrocirculation) and in the microcirculatory blood flow (i.e., the microcirculation) have been described. However, the presence and degree of microcirculatory failure are in part independent from systemic macrohemodynamic variables. Macrocirculatory and microcirculatory failure can independently induce organ dysfunction. We review current diagnostic and therapeutic approaches for the assessment and optimization of both the macrocirculation and the microcirculation in septic shock. There are various technologies for the determination of macrocirculatory hemodynamic variables. We discuss the data on early goal-directed therapy for the resuscitation of the macrocirculation. In addition, we describe the concept of “individualized goal-directed hemodynamic therapy.” Technologies to assess the local microcirculation are also available. However, adequate resuscitation goals for the optimization of the microcirculation still need to be defined. At present, we are not ready to specifically monitor and target the microcirculation in clinical routine outside studies. In the future, concepts for an integrative approach for individualized hemodynamic management of the macrocirculation and in parallel the microcirculation might constitute a huge opportunity to define additional resuscitation end points in septic shock.

Platelet-endothelial cell interaction in pulmonary microcirculation: the role of PARS

Accumulation of platelets might contribute to acute lung injury during systemic inflammation. The aim of the study was to elucidate the role of the poly (ADP-ribose) synthetase, a nucleotide-polymerizising enzyme, in mediation of platelet-endothelial cell interaction through regulation of adhesion molecules within the pulmonary microcirculation during endotoxemia. We used in vivo fluorescence microscopy to quantify kinetics of fluorescently labeled erythrocytes and platelets in rabbit pulmonary arterioles and venules. Six hours after onset of endotoxin infusion we observed a massive interaction of platelets with the microvascular endothelial cells, whereas under control conditions, no platelet sequestration was measured. An up-regulation of P- and E-selectin was detected in lung tissue following endotoxin infusion by immunohistochemistry and Western blot analysis. Blockade of endothelial P-selectin with fucoidin resulted in a reduction of the endotoxin-induced platelet-endothelial cell interaction. Inhibition of poly (ADP-ribose) synthetase by 3-aminobenzamide inhibited the endotoxin-induced expression of endothelial P- and E-selectin and the subsequent recruitment of platelets. In summary, we provide first in vivo evidence that platelets accumulate in pulmonary microcirculation following endotoxemia. Poly (ADP-ribose) synthetase seems to mediate this platelet-endothelial cell interaction via P- and E-selectin expressed on the surface of microvascular endothelium.

Glycocalyx degradation causes microvascular perfusion failure in the ex vivo perfused mouse lung: hydroxyethyl starch 130/0.4 pretreatment attenuates this response.

The endothelial glycocalyx (GLX) is pivotal to vascular barrier function. We investigated the consequences of GLX degradation on pulmonary microvascular perfusion and, prompted by evidence that hydroxyethyl starch (HES) improves microcirculation, studied the effects of two HES preparations during GLX diminution. C57 BL/6 black mice lungs were explanted and perfused with 1-mL/min buffer solution containing autologous erythrocytes (red blood cells) at a hematocrit of 5%. Microvessel perfusion was quantified by video fluorescence microscopy at 0 and 90 min. To register interstitial edema, alveolar septal width was quantified. Pulmonary artery pressure (PAP), airway pressure, and left atrial pressure were recorded continuously. Lungs were randomly assigned to four groups (each n = 5): (i) control: no treatment, (ii) HEP1: heparinase I (1 mU/mL) was injected for GLX degradation, (iii) HES 130, and (iv) HES 200: one third of perfusion fluid was exchanged for 6% HES 130/0.4 or 10% HES 200/0.5 before GLX degradation. Analysis of variance on ranks and pairwise multiple comparisons were used for statistics, P < 0.05. Compared with control, GLX degradation effected perfusion failure in microvessels, increased PAP, and facilitated interstitial edema formation after a 90-min period of perfusion. In contrast to HES 200/0.5, pretreatment with HES 130/0.4 attenuated all of these consequences. Sequelae of GLX degradation in lung include perfusion failure in microvessels, interstitial edema formation, and increase in PAP. We assume that these effects are a consequence of vascular barrier dysfunction. Beneficial effects of HES 130/0.4 are presumably a result of its lower red blood cell bridging capacity compared with HES 200/0.5. ABBREVIATIONS ESL—endothelial surface layer FACS—fluorescence-activated cell sorting FITC—fluorescein isothiocyanate GLX—endothelial glycocalyx HEP1—heparinase I HPMECs—human pulmonary microvascular endothelial cells HES—hydroxyethyl starch HS—heparan sulfate PAP—pulmonary artery pressure MFI—mean fluorescence intensity RBC—red blood cell VRBC—red blood cell velocity

Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?

Objectives:In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals. Design:Prospective, randomized animal study. Setting:University animal research laboratory. Subjects:Thirty domestic pigs. Interventions:After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal. Measurements and Main Results:Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (–90.76% [study group] vs –130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025). Conclusions:Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.

Tetrastarch sustains pulmonary microvascular perfusion and gas exchange during systemic inflammation

Objective: According to Ficks law of diffusion, gas exchange depends on the size and thickness of the blood perfused alveolocapillary membrane. Impairment of either one is tenuous. No data are available concerning the impact of hydroxyethyl starches and saline on pulmonary microperfusion and gas exchange during systemic inflammation. Design: Prospective, randomized, controlled experimental study. Setting: University research laboratory. Subjects: Thirty-two anesthetized rabbits assigned to four groups (n = 8). Interventions: Except for the control group, systemic inflammation was induced by lipopolysaccharide. Fluid resuscitation was performed with saline alone or in conjunction with tetrastarch or pentastarch. Pulmonary microcirculation was analyzed at 0 hr and 2 hrs using intravital microscopy. Thickness of the alveolocapillary membrane was measured using electron microscopy. Measurements and Main Results: Macrohemodynamics were stable in all groups. In pulmonary arterioles, lipopolysaccharide reduced the erythrocyte velocity and impeded the microvascular decrease of the hematocrit in the saline and pentastarch group. In contrast, infusion of tetrastarch normalized these perfusion parameters. In capillaries, lipopolysaccharide decreased the functional capillary segment density and the capillary perfusion index, which was prevented by both starches. However, compared with saline and pentastarch, treatment with tetrastarch prevented the lipopolysaccharide-induced reduction of the capillary erythrocyte flux and inversely reduced the erythrocyte capillary transit time. Thickening of alveolocapillary septae after lipopolysaccharide application was solely observed in the saline and pentastarch group. In contrast to pentastarch and saline, the application of tetrastarch prevented the lipopolysaccharide-induced increase of the alveoloarterial oxygen difference. Conclusions: Tetrastarch sustains pulmonary gas exchange during experimental systemic inflammation more effectively than saline and pentastarch by protecting the diffusion distance and the size of the microvascular gas exchange surface. Improved capillary perfusion resulting from tetrastarch therapy, which is typically applied to increase blood pressure, may according to the Ohms law locally decrease hydrostatic perfusion pressures in the pulmonary microvasculature during systemic inflammation.