Adjuvants for balanced anesthesia in ambulatory surgery.

Balanced anesthesia relies on the simultaneous administration of different drugs to attain an anesthetic state. The classic triad of anesthesia is a combination of a hypnotic, an analgesic, and a neuromuscular blocker. It is predominantly the analgesic pillar of this triad that became more and more supported by adjuvant therapy. The aim of this approach is to evolve into an opioid-sparing technique to cope with undesirable side effects of the opioids and is fueled by the opioid epidemic. The optimal strategy for balanced general anesthesia in ambulatory surgery must aim for a transition to a multimodal analgesic regimen dealing with acute postoperative pain and ideally reduce the most common adverse effects patients are faced with at home; sore throat, delayed awakening, memory disturbances, headache, nausea and vomiting, and negative behavioral changes. Over the years, this continuum of "multimodal general anesthesia" adopted many drugs with different modes of action. This review focuses on the most recent evidence on the different adjuvants that entered clinical practice and gives an overview of the different mechanisms of action, the potential as opioid-sparing or hypnotic-sparing drugs, and the applicability specifically in ambulatory surgery.

Prospective audit on fasting status of elective ambulatory surgery patients, correlated to gastric ultrasound.

INTRODUCTION: Recent guidelines advocate a preoperative fasting interval of 6 h for solid food, 4 h for breast milk and 2 h for clear fluids. Long nil per mouth intervals give rise to complications and discomfort in the perioperative period. Gastric ultrasound is easily accessible and generates reliable information about gastric content. PATIENTS AND METHODS: One hundred patients were offered a questionnaire regarding preoperative fasting. Important outcome measures were hour of last meal, last clear fluids intake, the source of preoperative information. Gastric ultrasound was performed in prone position and lateral decubitus. RESULTS: The mean duration of fasting for solid food was 13h29 and 9h51 for clear fluids. 48% of patients were well aware of the correct fasting guidelines. The most frequent source of information was the preoperative phone call. Gastric ultrasound only found insignificant amounts of gastric content. DISCUSSION: Too few patients are aware of the correct guidelines or fear complications and therefore adhere to the nil per mouth from midnight as most conservative measure. A phone call informing patients about the hour of surgery and allowing clear fluid intake until 2 h before surgery, is still not convincing enough. Some health care providers advise their patients the nil per mouth from midnight rule, due to risk of interfering with the operating room schedule. CONCLUSION: It is still difficult to implement liberal intake of clear fluids according to current guidelines. Ambulatory surgery patients have long fasting intervals with decrease of subjective well-being and increased incidence of hunger and thirst.

Application of a Volumetric Absorptive Microsampling (VAMS)-Based Method for the Determination of Paracetamol and Four of its Metabolites as a Tool for Pharmacokinetic Studies in Obese and Non-Obese Patients.

BACKGROUND: The pharmacokinetic (PK) profile of a drug is influenced by several factors, which can lead to a suboptimal dosing regimen in specific patient populations. As obesity becomes increasingly prevalent, it is important that optimized dosing schemes are available for these patients. To set up such dosing schemes, PK studies should be performed in this population. Regarding paracetamol (acetaminophen [APAP]), obese patients would benefit from a tailored dosing scheme, as both the volume of distribution and metabolism are increased compared with non-obese patients. This includes metabolism by cytochrome P450 2E1, which is involved in APAP-associated hepatotoxicity. To decrease the burden for patients in these PK studies, finger-prick sampling could be used. OBJECTIVE: The aim of this study was to compare the quantitative determination of APAP and four metabolites in different blood-based matrices and to determine if capillary dried blood samples, collected directly following finger-prick, could serve as a tool to investigate APAP PK in obese and non-obese patients. METHODS: In this study, we performed a clinical validation of methods for the determination of APAP and four of its metabolites (APAP-glucuronide, APAP-sulfate, APAP-mercapturate, and APAP-cysteine) in blood, plasma, and dried blood. The latter was obtained by volumetric absorptive microsampling (VAMS), either starting from the venous blood or collected directly following a finger-prick. Results were compared between the different matrices and, in addition, blood:plasma (B:P) ratios were determined for the different analytes. RESULTS: Liquid and dried venous blood results were in good agreement. Furthermore, differences between capillary (finger-prick) and venous VAMS blood samples remained limited for most analytes. However, for APAP-cysteine, caution should be paid to the interpretation of concentrations in (dried) blood. With the exception of APAP, concentrations were higher in plasma compared with blood, with B:P ratios ranging between 0.52 and 0.65. A time-dependent change in median B:P ratio was observed for APAP and APAP-cysteine. Additionally, a time-dependent trend was seen for APAP, as well as for APAP-glucuronide and APAP-mercapturate, for the distribution between capillary and venous blood. CONCLUSIONS: We demonstrated that finger-prick sampling is a viable alternative to conventional venous blood sampling to investigate the PK of APAP and its metabolites in obese and non-obese patients.

Effect of norepinephrine infusion on hepatic blood flow and its interaction with somatostatin: an observational cohort study.

BACKGROUND: Norepinephrine (NE) is a α1-adrenergic mediated vasopressor and a key player in the treatment of perioperative hypotension. Apart from modulating systemic hemodynamics, NE may also affect regional blood flow, such as the hepatic circulation, which contains a wide variety of adrenergic receptors. It may alter regional vascular tonus and hepatic blood flow (HBF) by reducing portal vein flow (PVF) or hepatic arterial flow (HAF). The aim of this study was to assess the effects of NE on HBF. METHODS: Patients scheduled for pancreaticoduodenectomy were included. All patients received standardized anesthetic care using propofol and remifentanil and were hemodynamically stabilized using a goal-directed hemodynamic strategy guided by Pulsioflex™. On surgical indication, somatostatin (SOMATO) was given to reduce pancreatic secretion. HBF measurements were performed using transit-time ultrasound (Medistim™). Baseline hemodynamic and HBF measurements were made after pancreatectomy, at T1. Afterwards, NE infusion was initiated to increase mean arterial pressure (MAP) by 10 - 20% of baseline MAP (T2) and by 20 - 30% of baseline MAP (T3). HBF and hemodynamic measurements were performed simultaneously at these three time-points. RESULTS: A total of 28 patients were analyzed. Administration of NE significantly increased MAP but had no effect on cardiac index. NE infusion reduced total HBF in all patients (p < 0.01) by a reduction HAF (p < 0.01), while the effect on PVF remained unclear. Post-hoc analysis showed that SOMATO-treated patients had a significant lower PVF at baseline (p < 0.05), which did not change during NE infusion. In these patients, reduction of total HBF was primarily related to a reduction of HAF (p < 0.01). In untreated patients, NE infusion reduced total HBF both by a reduction HAF (p < 0.01) and PVF (p < 0.05). CONCLUSION: Administration of NE reduced total HBF, by decreasing HAF, while the effect on PVF remained unclear. SOMATO-treated patients had a lower PVF at baseline, which remained unaffected during NE infusion. In these patients the decrease in total HBF with NE was entirely related to the decrease in HAF. In SOMATO-untreated patients PVF also significantly decreased with NE. TRIAL REGISTRATION: Study protocol EC: 2019/0395. EudraCT n°: 2018-004,139-66 (25 - 03 - 2019). Clin.trail.gov: NCT03965117 (28 - 05 - 2019).

Laryngeal mask airway protector generates higher oropharyngeal leak pressures compared to the laryngeal mask airway supreme: A randomized clinical trial in the ambulatory surgery unit.

BACKGROUND AND AIMS: The Laryngeal Mask Airway (LMA) Protector™ is one of the latest introduced supraglottic airway devices. It provides access and functional separation of the respiratory and digestive tracts. Compared to the LMA Supreme™, it has two digestive ports, one to provide suction in the pharyngeal region and one for gastric tube insertion. High oropharyngeal leak pressure is a marker for safe ventilation when using LMA devices. We hypothesized that oropharyngeal leak pressure of the LMA Protector™ is 5 cm H2O higher than the oropharyngeal leak pressure of the LMA Supreme™ at various cuff volumes. Secondary outcome measures were ease of insertion of both masks, fiberoptic confirmation of correct positioning, failures of insertion, presence of blood staining, sore throat, presence of air leak and insertion time. MATERIAL AND METHODS: American Society of Anesthesiologists (ASA) I-III patients aged >18 years, scheduled for elective minor ambulatory surgery under general anesthesia with a LMA were included. Patients were randomized in the LMA Protector™ or LMA Supreme™ group based on a computer-generated random sequence table. After general anesthesia induction, oropharyngeal leak pressures were measured. RESULTS: Oropharyngeal leak pressures were significantly higher (P < 0.0001) for LMA Protector™ compared to LMA Supreme™ at different cuff volumes and a cuff pressure of 65 cm H2O. Insertion time was significantly higher for the LMA Protector™ (29 sec) [interquartile range (IQR) 23, 35] compared to the LMA Supreme™ (19 sec) (IQR 16, 22) (P < 0.0001). There were no statistically significant differences in ease of insertion (number of attempts for succesful positioning), failures of insertion, presence of blood staining, sore throat or presence of air leak. CONCLUSION: Oropharyngeal leak pressures were consistently higher (>5 cm H2O) for LMA Protector™ compared to LMA Supreme™. LMA Protector™, therefore, allows effective ventilation at higher airway pressures than LMA Supreme™. TRIAL REGISTRATION: http://clinicaltrials.gov.NCT03462550.

Prolonging deep inspiration breath-hold time to 3 min during radiotherapy, a simple solution.

BACKGROUND AND PURPOSE: Deep inspiration breath-hold is an established technique to reduce heart dose during breast cancer radiotherapy. However, modern breast cancer radiotherapy techniques with lymph node irradiation often require long beam-on times of up to 5 min. Therefore, the combination with deep inspiration breath-hold (DIBH) becomes challenging. A simple support technique for longer duration deep inspiration breath-hold (L-DIBH), feasible for daily use at the radiotherapy department, is required to maximize heart sparing. MATERIALS AND METHODS: At our department, a new protocol for multiple L-DIBH of at least 2 min and 30 s was developed on 32 healthy volunteers and validated on 8 breast cancer patients during radiotherapy treatment, using a pragmatic process of iterative development, including all major stakeholders. Each participant performed 12 L-DIBHs, on 4 different days. Different methods of pre-oxygenation and voluntary hyperventilation were tested, and scored on L-DIBH duration, ease of use, and comfort. RESULTS: Based on 384 L-DIBHs from 32 healthy volunteers, voluntary hyperventilation for 3 min whilst receiving high-flow nasal oxygen at 40 L/min was the most promising technique. During validation, the median L-DIBH duration in prone position of 8 breast cancer patients improved from 59 s without support to 3 min and 9 s using the technique (p < 0.001). CONCLUSION: A new and simple L-DIBH protocol was developed feasible for daily use at the radiotherapy center.

The Obese Patient: Facts, Fables, and Best Practices.

The prevalence of obesity continues to rise worldwide, and anesthesiologists must be aware of current best practices in the perioperative management of the patient with obesity. Obesity alters anatomy and physiology, which complicates the evaluation and management of obese patients in the perioperative setting. Gastric point-of-care ultrasound (PoCUS) is a noninvasive tool that can be used to assess aspiration risk in the obese patient by evaluating the quantity and quality of gastric contents. An important perioperative goal is adequate end-organ perfusion. Standard noninvasive blood pressure (NIBP) is our best available routine surrogate measurement, but is vulnerable to greater inaccuracy in patients with obesity compared to the nonobese population. Current NIBP methodologies are discussed. Obese patients are at risk for wound and surgical site infections, but few studies conclusively guide the exact dosing of intraoperative prophylactic antibiotics for them. We review evidence for low-molecular-weight heparins and weight-based versus nonweight-based administration of vasoactive medications. Finally, intubation and extubation of the patient with obesity can be complicated, and evidence-based strategies are discussed to mitigate danger during intubation and extubation.

Effects of propofol and sevoflurane on hepatic blood flow: a randomized controlled trial.

BACKGROUND: Maintaining adequate perioperative hepatic blood flow (HBF) supply is essential for preservation of postoperative normal liver function. Propofol and sevoflurane affect arterial and portal HBF. Previous studies have suggested that propofol increases total HBF, primarily by increasing portal HBF, while sevoflurane has only minimal effect on total HBF. Primary objective was to compare the effect of propofol (group P) and sevoflurane (group S) on arterial, portal and total HBF and on the caval and portal vein pressure during major abdominal surgery. The study was performed in patients undergoing pancreaticoduodenectomy because - in contrast to hepatic surgical procedures - this is a standardized surgical procedure without potential anticipated severe hemodynamic disturbances, and it allows direct access to the hepatic blood vessels. METHODS: Patients were randomized according to the type of anesthetic drug used. For both groups, Bispectral Index (BIS) monitoring was used to monitor depth of anesthesia. All patients received goal-directed hemodynamic therapy (GDHT) guided by the transpulmonary thermodilution technique. Hemodynamic data were measured, recorded and guided by Pulsioflex™. Arterial, portal and total HBF were measured directly, using ultrasound transit time flow measurements (TTFM) and were related to hemodynamic variables. RESULTS: Eighteen patients were included. There was no significant difference between groups in arterial, portal and total HBF. As a result of the GDHT, pre-set hemodynamic targets were obtained in both groups, but MAP was significantly lower in group S (p = 0.01). In order to obtain these pre-set hemodynamic targets, group S necessitated a significantly higher need for vasopressor support (p < 0.01). CONCLUSION: Hepatic blood flow was similar under a propofol-based and a sevoflurane-based anesthetic regimen. Related to the application of GDHT, pre-set hemodynamic goals were maintained in both groups, but sevoflurane-anaesthetized patients had a significantly higher need for vasopressor support. TRIAL REGISTRATION: Study protocol number is AGO/2017/002 - EC/2017/0164. EudraCT number is 2017-000071-90. Clin.trail.gov, NCT03772106 , Registered 4/12/2018, retrospective registered.

Somatostatin as Inflow Modulator in Liver-transplant Recipients With Severe Portal Hypertension: A Randomized Trial.

OBJECTIVE: To investigate the safety and efficacy of somatostatin as liver inflow modulator in patients with end-stage liver disease (ESLD) and clinically significant portal hypertension (CSPH) undergoing liver transplantation (LT) (ClinicalTrials.gov number,01290172). BACKGROUND: In LT, portal hyperperfusion can severely impair graft function and survival, mainly in cases of partial LT. METHODS: Thirty-three patients undergoing LT for ESLD and CSPH were randomized double-blindly to receive somatostatin or placebo (2:1). The study drug was administered intraoperatively as 5-mL bolus (somatostatin: 500 µg), followed by a 2.5 mL/h infusion (somatostatin: 250 µg/h) for 5 days. Hepatic and systemic hemodynamics were measured, along with liver function tests and clinical outcomes. The ischemia-reperfusion injury (IRI) was analyzed through histological and protein expression analysis. RESULTS: Twenty-nine patients (18 receiving somatostatin, 11 placebo) were included in the final analysis. Ten patients responded to somatostatin bolus, with a significant decrease in hepatic venous portal gradient (HVPG) and portal flow of -28.3% and -29.1%, respectively. At graft reperfusion, HVPG was lower in patients receiving somatostatin (-81.7% vs -58.8%; P = 0.0084), whereas no difference was observed in the portal flow (P = 0.4185). Somatostatin infusion counteracted the decrease in arterial flow (-10% vs -45%; P = 0.0431). There was no difference between the groups in the severity of IRI, incidence of adverse events, long-term complications, graft, and patient survival. CONCLUSIONS: Somatostatin infusion during LT in patients with CSPH is safe, reduces the HVPG, and preserves the arterial inflow to the graft. This study establishes the efficacy of somatostatin as a liver inflow modulator.

International multicenter observational study on assessment of ventilatory management during general anaesthesia for robotic surgery and its effects on postoperative pulmonary complication (AVATaR): study protocol and statistical analysis plan.

INTRODUCTION: Robotic-assisted surgery (RAS) has emerged as an alternative minimally invasive surgical option. Despite its growing applicability, the frequent need for pneumoperitoneum and Trendelenburg position could significantly affect respiratory mechanics during RAS. AVATaR is an international multicenter observational study aiming to assess the incidence of postoperative pulmonary complications (PPC), to characterise current practices of mechanical ventilation (MV) and to evaluate a possible association between ventilatory parameters and PPC in patients undergoing RAS. METHODS AND ANALYSIS: AVATaR is an observational study of surgical patients undergoing MV for general anaesthesia for RAS. The primary outcome is the incidence of PPC during the first five postoperative days. Secondary outcomes include practice of MV, effect of surgical positioning on MV, effect of MV on clinical outcome and intraoperative complications. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the Hospital Israelita Albert Einstein. The study results will be published in peer-reviewed journals and disseminated at international conferences. TRIAL REGISTRATION NUMBER: NCT02989415; Pre-results.

Postoperative complications in cardiac patients undergoing noncardiac surgery.

PURPOSE OF REVIEW: In this article we review the current knowledge on the underlying mechanisms of perioperative myocardial injury, the preoperative methods of predicting these complications, the diagnostic tools for detecting perioperative myocardial injuries, and the available protective strategies to prevent or attenuate the extent of myocardial injury. RECENT FINDINGS: The last years' new insights have provided a better understanding of the problem of perioperative myocardial injury and infarction. Specifically, the importance of early diagnosis and prompt treatment are increasingly getting attention. Concomitantly, the results of recent large multicenter studies have challenged classical therapeutic approaches in the perioperative treatment of cardiac patients undergoing noncardiac surgery. SUMMARY: These new insights will help to better tailor individual strategies to prevent or minimize perioperative cardiac complications. Especially, early diagnosis and intensification of treatment will get specific interest in the coming years.

Best anaesthetic drug strategy for morbidly obese patients.

PURPOSE OF REVIEW: The purpose of this review is to describe an evidence-based drug strategy applicable to any obese patient, rather than to present one standard 'ideal' anaesthetic drug combination. The ultimate choice of specific drugs in any given situation will depend upon clinician experience, patient specifics, and drug availability. The fundamental principle in anaesthesia for the obese patient is to use the shortest acting, least fat soluble agents to ensure rapid recovery to safe levels of alertness and mobility. RECENT FINDINGS: No new drugs have been introduced over the past few years, but we have seen an introduction of enhanced recovery after surgery-based protocols into bariatric surgery. Our understanding of how obesity affects pharmacokinetics/dynamics of our drugs is improving, with new and better use of established drugs. Allometric scaling is being tested in the different pharmacokinetic/dynamic models used in target controlled infusion devices, with improved performance as a result. Obstructive sleep apnoea has a significant impact upon outcome and utilization of clinical resources, including critical care beds. If an improved drug dosing strategy will reduce this impact, then this would be a step forward. SUMMARY: This review introduces newer findings to help us use anaesthetic and analgesic drugs more safely in the morbidly obese. However, there remain many areas of uncertainty with a lack of consensus on many issues.

Why hydroxyethyl starch solutions should NOT be banned from the operating room.

This review summarises the new insights into the physiology of perioperative fluid therapy and analyses recent studies of the safety of the use of HES solutions in the fluid management of critically ill patients. This analysis reveals a number of methodological issues in the three major studies that have initiated the recommendation of the European Medicine Agency to ban hydroxyethyl starches from clinical practice. It is concluded that, when used in the proper indication, and taking into account the recommended doses, hydroxyethyl starches continue to have a place in perioperative fluid management.

What the phlebologist should know about local anesthetics.

An increasing number of phlebological interventions are performed under local and tumescent anesthesia. Although the modern local anesthetic agents are generally perceived as being effective and safe drugs, the administration of these drugs may be associated with a number of adverse events. It is therefore mandatory that everyone who uses these compounds has insight into the pharmacological actions of these drugs and is capable of recognizing and adequately treating potential adverse events. The present narrative review summarizes the current knowledge on mechanisms of action of the most important local anesthetic drugs and reviews the potential adverse effects as well as their treatment.

Some pharmacokinetics of sevoflurane in a child with severe lipodystrophy.

Lipodystrophies are acquired or inherited disorders characterized in part by the selective loss of adipose tissue and hypertriglyceridemia. The present case report of 2 sevoflurane anesthetics given to a child with such a disorder, before and after correction of severe hypertriglyceridemia, illustrates the considerable effects of increased serum lipids and decreased fat stores on the pharmacokinetics of sevoflurane.

Laparoscopic evaluation shows deficiencies in memory ring deployment during small ventral hernia repair.

BACKGROUND: With the introduction of a self-expanding, memory-containing, circular hernia patch, surgeons have been enthusiastic about its use to repair ventral hernias smaller than 3 cm in diameter. The aim of this study was to evaluate the efficiency, reliability, and safety of the device laparoscopically with respect to adequate deployment of the patch. METHODS: During 1 year all patients with small ventral hernias were treated with this memory-containing patch and were inspected by laparoscopy. Just prior to insertion of the patch, remaining adhesions on top of the peritoneum were analyzed, as was the interference of the umbilical ligament. The final position of the patch was monitored, identifying the cupping phenomenon, exposure of the polypropylene to the viscera, and the amount of tension on the straps. All patients were followed for 2 years and postoperative complications and recurrence rate were monitored. RESULTS: Twenty-eight patients were operated on for repair of a small ventral hernia with laparoscopic control. Adhesions, not digitally palpable, that interfered with adequate patch deployment were observed in more than 80% of the cases. After a median follow-up of 25 months a 14.8% recurrence rate was observed. CONCLUSIONS: The patch, consisting of both polypropylene and ePTFE, leads to unacceptable morbidity and a high rate of recurrences. By laparoscopic evaluation, these recurrences are probably based on a combination of material characteristics and unavoidable technical errors.

Comparable results with 3-year follow-up for large-pore versus small-pore meshes in open incisional hernia repair.

BACKGROUND: Decreasing the amount of polypropylene by increasing pore size produces a lighter weight mesh that may improve tissue ingrowth and, functional properties of the abdominal wall and diminish mesh-related complications. It was the aim of this prospective observational cohort study to analyze the outcome of incisional hernia repair using small-pore versus large-pore meshes and using a standardized, open, retromuscular surgical technique. METHODS: Across a 6-year period we analyzed 205 patients treated with a heavyweight mesh (group I) and 235 patients treated with a large-pore mesh (group II) for incisional hernias. Patients with a body mass index greater than 40 kg/m(2) and patients with hernias with a transverse diameter of more than 10 cm were not treated by a retromuscular mesh repair and are not included in this analysis. Recurrent incisional hernias also were not included. Both groups had 3 years of follow-up. Patients were evaluated for pain, discomfort, feeling of foreign material, and recurrences. RESULTS: Pre-operative characteristics were comparable between the groups, including body mass index, diabetes, and smoking. The mean total hernia surface was 56 cm(2) for group I versus 48 cm(2) in group II. The mesh surface area was 448 cm(2) for group I and 425 cm(2) for group II. Considering pain scores, there was only a minor difference between the 2 groups at 1-month follow-up, at which time, the Visual Analogue Scale was 5.8 in group I and 4.9 in group II (P = .16). All other scores were comparable between the groups. In group I, 7 recurrences (3.4%) were recorded after 3 years, of which 6 were already apparent 1 year after initial repair. In group II, 9 recurrences (3.8%) were diagnosed, again 6 within the first year after repair. CONCLUSION: Large-pore meshes can be used safely for open primary incisional hernia repair with an equal outcome compared with small-pore meshes in nonobese patients with defects smaller than 10 cm in width, in regard to both recurrence rates and chronic discomfort.