Chronic post amputation pain: pathophysiology and prevention options for a heterogenous phenomenon.

PURPOSE OF REVIEW: Chronic postamputation pain (cPAP) remains a clinical challenge, and current understanding places a high emphasis on prevention strategies. Unfortunately, there is still no evidence-based regimen to reliably prevent chronic pain after amputation. RECENT FINDINGS: Risk factors for the development of phantom limb pain have been proposed. Analgesic preventive interventions are numerous and no silver bullet has been found. Novel techniques such as neuromodulation and cryoablation have been proposed. Surgical techniques focusing on reimplantation of the injured nerve might reduce the incidence of phantom limb pain after surgery. SUMMARY: Phantom limb pain is a multifactorial process involving profound functional and structural changes in the peripheral and central nervous system. These changes interact with individual medical, psychosocial and genetic patient risk factors. The patient collective of amputees is very heterogeneous. Available evidence suggests that efforts should focus on prevention of phantom limb pain, since treatment is notoriously difficult. Questions as yet unanswered include the evidence-base of specific analgesic interventions, their optimal "window of opportunity" where they may be most effective, and whether patient stratification according to biopsychosocial risk factors can help guide preventive therapy.

Effect of the machine learning-derived Hypotension Prediction Index (HPI) combined with diagnostic guidance versus standard care on depth and duration of intraoperative and postoperative hypotension in elective cardiac surgery patients: HYPE-2 - study protocol of a randomised clinical trial.

INTRODUCTION: Hypotension is common during cardiac surgery and often persists postoperatively in the intensive care unit (ICU). Still, treatment is mainly reactive, causing a delay in its management. The Hypotension Prediction Index (HPI) can predict hypotension with high accuracy. Using the HPI combined with a guidance protocol resulted in a significant reduction in the severity of hypotension in four non-cardiac surgery trials. This randomised trial aims to evaluate the effectiveness of the HPI in combination with a diagnostic guidance protocol on reducing the occurrence and severity of hypotension during coronary artery bypass grafting (CABG) surgery and subsequent ICU admission. METHODS AND ANALYSIS: This is a single-centre, randomised clinical trial in adult patients undergoing elective on-pump CABG surgery with a target mean arterial pressure of 65 mm Hg. One hundred and thirty patients will be randomly allocated in a 1:1 ratio to either the intervention or control group. In both groups, a HemoSphere patient monitor with embedded HPI software will be connected to the arterial line. In the intervention group, HPI values of 75 or above will initiate the diagnostic guidance protocol, both intraoperatively and postoperatively in the ICU during mechanical ventilation. In the control group, the HemoSphere patient monitor will be covered and silenced. The primary outcome is the time-weighted average of hypotension during the combined study phases. ETHICS AND DISSEMINATION: The medical research ethics committee and the institutional review board of the Amsterdam UMC, location AMC, the Netherlands, approved the trial protocol (NL76236.018.21). No publication restrictions apply, and the study results will be disseminated through a peer-reviewed journal. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register (NL9449), ClinicalTrials.gov (NCT05821647).

Feasibility to estimate mean systemic filling pressure with inspiratory holds at the bedside.

Background: A decade ago, it became possible to derive mean systemic filling pressure (MSFP) at the bedside using the inspiratory hold maneuver. MSFP has the potential to help guide hemodynamic care, but the estimation is not yet implemented in common clinical practice. In this study, we assessed the ability of MSFP, vascular compliance (Csys), and stressed volume (Vs) to track fluid boluses. Second, we assessed the feasibility of implementation of MSFP in the intensive care unit (ICU). Exploratory, a potential difference in MSFP response between colloids and crystalloids was assessed. Methods: This was a prospective cohort study in adult patients admitted to the ICU after cardiac surgery. The MSFP was determined using 3-4 inspiratory holds with incremental pressures (maximum 35 cm H2O) to construct a venous return curve. Two fluid boluses were administered: 100 and 500 ml, enabling to calculate Vs and Csys. Patients were randomized to crystalloid or colloid fluid administration. Trained ICU consultants acted as study supervisors, and protocol deviations were recorded. Results: A total of 20 patients completed the trial. MSFP was able to track the 500 ml bolus (p < 0.001). In 16 patients (80%), Vs and Csys could be determined. Vs had a median of 2029 ml (IQR 1605-3164), and Csys had a median of 73 ml mmHg-1 (IQR 56-133). A difference in response between crystalloids and colloids was present for the 100 ml fluid bolus (p = 0.019) and in a post hoc analysis, also for the 500 ml bolus (p = 0.010). Conclusion: MSFP can be measured at the bedside and provides insights into the hemodynamic status of a patient that are currently missing. The clinical feasibility of Vs and Csys was judged ambiguously based on the lack of required hemodynamic stability. Future studies should address the clinical obstacles found in this study, and less-invasive alternatives to determine MSFP should be further explored. Clinical Trial Registration: ClinicalTrials.gov Identifier NCT03139929.

Autologous red blood cell transfusion does not result in a more profound increase in pulmonary capillary wedge pressure compared to saline in critically ill patients: A randomized crossover trial.

BACKGROUND AND OBJECTIVES: Transfusion-associated circulatory overload (TACO) is a major cause of severe transfusion-related morbidity. Transfusion of red blood cells (RBCs) has been shown to induce hydrostatic pressure overload. It is unclear which product-specific factors contribute. We set out to determine the effect of autologous RBC transfusion versus saline on pulmonary capillary wedge pressure (PCWP) change. MATERIALS AND METHODS: In a randomized crossover trial, patients who had undergone coronary bypass surgery were allocated to treatment post-operatively in the intensive care unit with either an initial 300 ml autologous RBC transfusion (salvaged during surgery) or 300 ml saline infusion first, followed by the other. Primary outcome was the difference in PCWP change. Secondary outcome measures were the difference in extra-vascular lung water index (EVLWI) and pulmonary vascular permeability index (PVPI). RESULTS: Change in PCWP was not higher after autologous RBC transfusion compared to saline (ΔPCWP 0.3 ± 0.4 vs. 0.1 ± 0.4 mmHg). ΔEVLWI and ΔPVPI were significantly decreased after autologous RBC transfusion compared to saline (ΔEVLWI -1.6 ± 0.6 vs. 0.2 ± 0.4, p = 0.02; ΔPVPI -0.3 ± 0.1 vs. 0.0 ± 0.1, p = 0.01). Haemodynamic variables and colloid osmotic pressure were not different for autologous RBC transfusion versus saline. CONCLUSION: Transfusion of autologous RBCs did not result in a more profound increase in PCWP compared to saline. RBC transfusion resulted in a decrease of EVLWI and PVPI compared to saline. Our data suggest that transfusing autologous RBCs may lead to less pulmonary oedema compared to saline. Future studies with allogeneic RBCs are needed to investigate other factors that may mediate the increase of PCWP, resulting in TACO.

Anesthesia Considerations in Infective Endocarditis.

The management of infective endocarditis is complex and inherently requires multidisciplinary cooperation. About half of all patients diagnosed with infective endocarditis will meet the criteria to undergo cardiac surgery, which regularly takes place in urgent or emergency settings. The pathophysiology and clinical presentation of infective endocarditis make it a unique disorder within cardiac surgery that warrants a thorough understanding of specific characteristics in the perioperative period. This includes, among others, echocardiography, coagulation, bleeding management, or treatment of organ dysfunction. In this narrative review article, the authors summarize the current knowledge on infective endocarditis relevant for the clinical anesthesiologist in perioperative management of respective patients. Furthermore, the authors advocate for the anesthesiologist to become a structural member of the endocarditis team.

Effect of a Machine Learning-Derived Early Warning System for Intraoperative Hypotension vs Standard Care on Depth and Duration of Intraoperative Hypotension During Elective Noncardiac Surgery: The HYPE Randomized Clinical Trial.

Importance: Intraoperative hypotension is associated with increased morbidity and mortality. A machine learning-derived early warning system to predict hypotension shortly before it occurs has been developed and validated. Objective: To test whether the clinical application of the early warning system in combination with a hemodynamic diagnostic guidance and treatment protocol reduces intraoperative hypotension. Design, Setting, and Participants: Preliminary unblinded randomized clinical trial performed in a tertiary center in Amsterdam, the Netherlands, among adult patients scheduled for elective noncardiac surgery under general anesthesia and an indication for continuous invasive blood pressure monitoring, who were enrolled between May 2018 and March 2019. Hypotension was defined as a mean arterial pressure (MAP) below 65 mm Hg for at least 1 minute. Interventions: Patients were randomly assigned to receive either the early warning system (n = 34) or standard care (n = 34), with a goal MAP of at least 65 mm Hg in both groups. Main Outcomes and Measures: The primary outcome was time-weighted average of hypotension during surgery, with a unit of measure of millimeters of mercury. This was calculated as the depth of hypotension below a MAP of 65 mm Hg (in millimeters of mercury) × time spent below a MAP of 65 mm Hg (in minutes) divided by total duration of operation (in minutes). Results: Among 68 randomized patients, 60 (88%) completed the trial (median age, 64 [interquartile range {IQR}, 57-70] years; 26 [43%] women). The median length of surgery was 256 minutes (IQR, 213-430 minutes). The median time-weighted average of hypotension was 0.10 mm Hg (IQR, 0.01-0.43 mm Hg) in the intervention group vs 0.44 mm Hg (IQR, 0.23-0.72 mm Hg) in the control group, for a median difference of 0.38 mm Hg (95% CI, 0.14-0.43 mm Hg; P = .001). The median time of hypotension per patient was 8.0 minutes (IQR, 1.33-26.00 minutes) in the intervention group vs 32.7 minutes (IQR, 11.5-59.7 minutes) in the control group, for a median difference of 16.7 minutes (95% CI, 7.7-31.0 minutes; P < .001). In the intervention group, 0 serious adverse events resulting in death occurred vs 2 (7%) in the control group. Conclusions and Relevance: In this single-center preliminary study of patients undergoing elective noncardiac surgery, the use of a machine learning-derived early warning system compared with standard care resulted in less intraoperative hypotension. Further research with larger study populations in diverse settings is needed to understand the effect on additional patient outcomes and to fully assess safety and generalizability. Trial Registration: ClinicalTrials.gov Identifier: NCT03376347.