Systemic Ropivacaine Concentrations Following Local Infiltration Analgesia and Femoral Nerve Block in Older Patients Undergoing Total Knee Arthroplasty.

Purpose: The study examined the pharmacokinetic profile of fixed formulation mixtures comprising 225 mg of ropivacaine for local infiltration analgesia with or without epinephrine, and femoral nerve block in older patients presenting for orthopedic surgery and explored potential influences of block type, age, and body weight on this profile. Patients and Methods: Twenty four patients scheduled for total knee arthroplasty were randomly assigned to three groups: femoral nerve block, local infiltration analgesia with epinephrine and local infiltration analgesia without epinephrine. Blood samples were collected at 10, 30, 60, and 120 min following the block and total plasma concentrations of ropivacaine were quantified by high performance liquid chromatography. Results: The mean individual peak total plasma concentrations of ropivacaine in local infiltration analgesia with and without epinephrine, and femoral nerve block group were 0.334, 0.490 and 0.545 µg mL-1 (p = 0.16). Local infiltration with epinephrine group had significantly lower plasma ropivacaine concentrations at 30, 60 and 120 minutes. The plasma ropivacaine concentrations exceeded 2.2 µg mL-1 in one patient. Age, but not body weight, had a moderate correlation with peak plasma ropivacaine concentration (r = 0.37, p = 0.08). Conclusion: Administration of a fixed 225 mg dose of ropivacaine for local infiltration analgesia with epinephrine and femoral nerve block results in plasma ropivacaine concentrations below the toxicity threshold, indicating their safety. The use of local infiltration analgesia with epinephrine provides a greater safety margin, as local infiltration analgesia without epinephrine may lead to ropivacaine concentrations associated with symptoms of local anesthetic toxicity.

Infrared Thermography Imaging for Assessment of Peripheral Perfusion in Patients with Septic Shock.

Skin temperature changes can be used to assess peripheral perfusion in circulatory shock patients. However, research has been limited to point measurements from acral parts of the body. Infrared thermography allows non-invasive evaluation of temperature distribution over a larger surface. Our study aimed to map thermographic patterns in the knee and upper thigh of 81 septic shock patients within 24 h of admission and determine the relationship between skin temperature patterns, mottling, and 28-day mortality. We extracted skin temperature measurements from zones corresponding to mottling scores and used a linear mixed model to analyze the distribution of skin temperature in patients with different mottling scores. Our results showed that the distribution of skin temperature in the anterior thigh and knee is physiologically heterogeneous and has no significant association with mottling or survival at 28 days. However, overall skin temperature of the anterior thigh and knee is significantly lower in non-survivors when modified by mottling score. No differences were found in skin temperature between the survivor and non-survivor groups. Our study shows the potential usefulness of infrared thermography in evaluating skin temperature patterns in resuscitated septic shock patients. Overall skin temperature of the anterior thigh and knee may be an important indicator of survival status when modified by mottling score.

Relationship of mottling score, skin microcirculatory perfusion indices and biomarkers of endothelial dysfunction in patients with septic shock: an observational study.

BACKGROUND: In patients with septic shock, the skin is often chosen for the evaluation of peripheral perfusion and oxygenation. Changes in skin microcirculatory vessel oxygen saturation and relative hemoglobin concentration can be described using a mottling score or captured with hyperspectral imaging. However, the effectiveness of the mottling score in assessing microcirculation remains to be shown. We hypothesize that the mottling score in patients with septic shock is related to skin microcirculatory perfusion indices quantified by hyperspectral imaging, biomarkers that reflect endothelium activation and damage, and clinical outcome. METHODS: Hyperspectral imaging of the knee area was performed in 95 intensive care patients with septic shock enrolled in a single-center observational study to obtain relative oxy/deoxyhemoglobin concentration values and construct anatomical maps of skin microcirculatory saturation. The blood was sampled to obtain concentrations of thrombomodulin, plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), angiopoietin-2, and syndecan-1. The spectrophotometrically obtained skin microvascular perfusion indices were compared to the mottling score and biomarker concentration. The association between mottling score, skin microcirculatory perfusion indices, and 28-day mortality was also analyzed. RESULTS: Microcirculatory oxygen saturation was significantly lower and total hemoglobin concentration was significantly higher in patients with a mottling score of 2 compared to those with a score of 0 (p = 0.02), with no difference between other scores. We found an association between microcirculatory oxygen saturation and PAI-1 levels (rho = - 0.3; p = 0.007). Increased mottling score and decreased microcirculatory oxygen saturation were predictive of 28-day mortality (mottling score 2 vs 0: OR 15.31, 95% CI 4.12-68.11; microcirculatory oxygen saturation: OR 0.90, 95% CI 0.85-0.95). Endothelial biomarkers did not increase the predictive value of skin microcirculatory perfusion indices. CONCLUSIONS: Higher mottling scores are associated with lower microcirculatory oxygen saturation but with significant overlap between scores. Microcirculatory oxygen saturation is a quantitative measure of peripheral oxygenation and is more specific than the mottling score in predicting 28-day mortality.

Impaired vascular reactivity in sepsis - a systematic review with meta-analysis.

INTRODUCTION: Vascular dysfunction due to reduced nitric oxide bioavailability plays an important role in the pathogenesis of sepsis. This meta-analysis examines evidence from published literature to evaluate whether in the adult population the presence/severity of sepsis is associated with impaired vasoreactivity. MATERIAL AND METHODS: We performed a search of the Medline, Scopus, and EMBASE databases to identify observational studies using measurement of reactive hyperaemia in adult patients with sepsis. After data extraction using predefined protocol, qualitative synthesis of findings was performed regarding consistency of findings between methods, evidence of association between vascular reactivity and severity of sepsis, multiple organ failure, and death. A meta-analyses of standardised mean differences in vasoreactivity between groups was performed, in which data were available for relevant outcomes. RESULTS: Eighteen studies using four methods to measure vascular reactivity from a total of 466 were included in the analysis. The pooled standardised mean difference estimate showed that septic patients had less reactive hyperaemia than controls (-2.59, 95% CI: -3.46 to -1.72; p < 0.00001), and peak hyperaemic blood flow was lower in patients with sepsis than in the control group (SMD = -1.42, 95% CI: -2.14 to -0.70; p = 0.0001). The combined SMD between non survivors and survivors was -0.36 (95% CI: -0.67 to -0.06; p = 0.02) for reactive hyperaemia and -0.70 (95% CI: -1.13 to -0.27; p = 0.001) for peak hyperaemic blood flow. CONCLUSIONS: Septic patients have attenuated vascular reactivity when compared to healthy volunteers. There are insufficient data indicating that these changes can identify patients at risk of worsening organ failure or death.

Impact of increased mean arterial pressure on skin microcirculatory oxygenation in vasopressor-requiring septic patients: an interventional study.

BACKGROUND: Heterogeneity of microvascular blood flow leading to tissue hypoxia is a common finding in patients with septic shock. It may be related to suboptimal systemic perfusion pressure and lead to organ failure. Mapping of skin microcirculatory oxygen saturation and relative hemoglobin concentration using hyperspectral imaging allows to identify heterogeneity of perfusion and perform targeted measurement of oxygenation. We hypothesized that increasing mean arterial pressure would result in improved oxygenation in areas of the skin with most microvascular blood pooling. METHODS: We included adult patients admitted to the intensive care unit within the previous 24 h with sepsis and receiving a noradrenaline infusion. Skin oxygen saturation was measured using hyperspectral imaging-based method at baseline and after the increase in mean arterial pressure by 20 mm Hg by titration of noradrenaline doses. The primary outcome was an increase in skin oxygen saturation depending upon disease severity. RESULTS: We studied 30 patients with septic shock. Median skin oxygen saturation changed from 26.0 (24.5-27.0) % at baseline to 30.0 (29.0-31.0) % after increase in mean arterial pressure (p = 0.04). After adjustment for baseline saturation, patients with higher SOFA scores achieved higher oxygen saturation after the intervention (r2 = 0.21; p = 0.02). Skin oxygen saturation measured at higher pressure was found to be marginally predictive of mortality (OR: 1.10; 95% CI 1.00-1.23; p = 0.053). CONCLUSIONS: Improvement of microcirculatory oxygenation can be achieved with an increase in mean arterial pressure in most patients. Response to study intervention is proportional to disease severity.

Association between increased arterial stiffness and clinical outcomes in patients with early sepsis: a prospective observational cohort study.

BACKGROUND: Conduit arteries, especially the aorta, play a major role in ensuring efficient cardiac function and optimal microvascular flow due to their viscoelastic properties. Studies in animals and on isolated arteries show that acute systemic inflammation can cause aortic stiffening which affects hemodynamic efficiency. Carotid-femoral pulse wave velocity, a measure of aortic stiffness, may be useful as a bedside investigational method in patients with early sepsis admitted to intensive care, as circulatory changes can lead to multiple organ failure and increased mortality. This study aims to investigate arterial stiffness in early sepsis and its association with clinical outcomes. METHODS: This prospective observational study included adult patients with severe sepsis or septic shock admitted to our intensive care unit (n = 45). Their carotid-femoral pulse wave velocity was measured within 24 h of admission. We assessed the progression of multiple organ as well as cardiovascular failure by sequential SOFA scores. Prediction models for the progression of multiple organ and cardiovascular failure were constructed using multivariate logistic regression with pulse wave velocity and vasopressor use as predictors. A Cox proportional hazards model was used to examine the relationship between pulse wave velocity and survival time. RESULTS: The median pulse wave velocity for the cohort was 14.6 (8.1-24.7) m/s. There was no association between pulse wave velocity and the progression of multiple organ failure, before or after adjustment for vasopressor use. No association was found between pulse wave velocity and subsequent improvement in cardiovascular failure in the subgroup of patients who had cardiovascular instability at baseline. Cox regression and survival analyses with age, APACHE II, and baseline SOFA as confounders showed a shorter hospital survival time for patients with pulse wave velocity > 24.7 m/s (HR = 9.45, 95% CI 1.24-72.2; P = 0.03). CONCLUSIONS: Patients with severe sepsis and septic shock admitted to intensive care have higher arterial stiffness than in the general population. No convincing association was found between pulse wave velocity at admission and the progression of multiple organ or cardiovascular failure, although the group with pulse wave velocity > 24.7 m/s had shorter survival time.