Parenteral, Non-Intravenous Analgesia in Acute Traumatic Pain-A Narrative Review Based on a Systematic Literature Search.

Traumatic pain is frequently encountered in emergency care and requires immediate analgesia. Unfortunately, most trauma patients report sustained pain upon arrival at and discharge from the Emergency Department. Obtaining intravenous access to administer analgesics can be time-consuming, leading to treatment delay. This review provides an overview of analgesics with both fast onset and parenteral, non-intravenous routes of administration, and also indicates areas where more research is required.

Adjunctive hyperbaric oxygen therapy in the management of severe lower limb soft tissue injuries: a systematic review.

PURPOSE: Traumatic crush injuries of the lower limb often accompany severe complications. The incorporation of hyperbaric oxygen therapy to standard trauma care may have the potential to diminish injury-related complications and improve outcome in such cases. This systematic review aims to evaluate the effectiveness of hyperbaric oxygen therapy in the management of severe lower limb soft tissue injuries. METHODS: The electronic databases Medline, Embase and Cochrane Library were searched to identify studies involving patients with crush-associated sever lower limb soft tissue injuries who received hyperbaric oxygen therapy in conjunction with standard trauma care. Relevant data on type of injury, hyperbaric oxygen therapy protocol and outcome related to wound healing were extracted. RESULTS: In total seven studies met the inclusion criteria, involving 229 patients. The studies included two randomized clinical trials, one retrospective cohort study, three case series and one case report. The randomized placebo-controlled clinical trial showed a significant increase in wound healing and decrease in the need for additional surgical interventions in the patient group receiving hyperbaric oxygen therapy when compared to those undergoing sham therapy. The randomized non-placebo-controlled clinical trial revealed that early hyperbaric oxygen therapy reduces tissue necrosis and the likelihood of long-term complications. The retrospective cohort study indicated that hyperbaric oxygen therapy effectively reduces infection rates and the need for additional surgical interventions. The case series and case report presented beneficial results with regard to wound healing when hyperbaric oxygen therapy was added to the treatment regimen. CONCLUSION: Hyperbaric oxygen therapy is generally considered a safe therapeutic intervention and seems to have a beneficial effect on wound healing in severe lower limb soft tissue injuries when implemented as an addition to standard trauma care.

Computer tomography perfusion patterns in iatrogenic cerebral arterial gas embolism: A retrospective cohort study.

PURPOSE: Cerebral arterial gas embolism (CAGE) occurs when air or medical gas enters the systemic circulation during invasive procedures and lodges in the cerebral vasculature. Non-contrast computer tomography (CT) may not always show intracerebral gas. CT perfusion (CTP) might be a useful adjunct for diagnosing CAGE in these patients. METHODS: This is a retrospective single-center cohort study. We included patients who were diagnosed with iatrogenic CAGE and underwent CTP within 24 h after onset of symptoms between January 2016 and October 2022. All imaging studies were evaluated by two independent radiologists. CTP studies were scored semi-quantitatively for perfusion abnormalities (normal, minimal, moderate, severe) in the following parameters: cerebral blood flow, cerebral blood volume, time-to-drain and time-to-maximum. RESULTS: Among 27 patient admitted with iatrogenic CAGE, 15 patients underwent CTP within the designated timeframe and were included for imaging analysis. CTP showed perfusion deficits in all patients except one. The affected areas on CTP scans were in general located bilaterally and frontoparietally. The typical pattern of CTP abnormalities in these areas was hypoperfusion with an increased time-to-drain and time-to-maximum, and a corresponding minimal decrease in cerebral blood flow. Cerebral blood volume was mostly unaffected. CONCLUSION: CTP may show specific perfusion defects in patients with a clinical diagnosis of CAGE. This suggests that CTP may be supportive in diagnosing CAGE in cases where no intracerebral gas is seen on non-contrast CT.

Benefits and harms of perioperative high fraction inspired oxygen for surgical site infection prevention: a protocol for a systematic review and meta-analysis of individual patient data of randomised controlled trials.

INTRODUCTION: The use of high fraction of inspired oxygen (FiO2) intraoperatively for the prevention of surgical site infection (SSI) remains controversial. Promising results of early randomised controlled trials (RCT) have been replicated with varying success and subsequent meta-analysis are equivocal. Recent advancements in perioperative care, including the increased use of laparoscopic surgery and pneumoperitoneum and shifts in fluid and temperature management, can affect peripheral oxygen delivery and may explain the inconsistency in reproducibility. However, the published data provides insufficient detail on the participant level to test these hypotheses. The purpose of this individual participant data meta-analysis is to assess the described benefits and harms of intraoperative high FiO2compared with regular (0.21-0.40) FiO2 and its potential effect modifiers. METHODS AND ANALYSIS: Two reviewers will search medical databases and online trial registries, including MEDLINE, Embase, CENTRAL, CINAHL, ClinicalTrials.gov and WHO regional databases, for randomised and quasi-RCT comparing the effect of intraoperative high FiO2 (0.60-1.00) to regular FiO2 (0.21-0.40) on SSI within 90 days after surgery in adult patients. Secondary outcome will be all-cause mortality within the longest available follow-up. Investigators of the identified trials will be invited to collaborate. Data will be analysed with the one-step approach using the generalised linear mixed model framework and the statistical model appropriate for the type of outcome being analysed (logistic and cox regression, respectively), with a random treatment effect term to account for the clustering of patients within studies. The bias will be assessed using the Cochrane risk-of-bias tool for randomised trials V.2 and the certainty of evidence using Grading of Recommendations, Assessment, Development and Evaluation methodology. Prespecified subgroup analyses include use of mechanical ventilation, nitrous oxide, preoperative antibiotic prophylaxis, temperature (<35°C), fluid supplementation (<15 mL/kg/hour) and procedure duration (>2.5 hour). ETHICS AND DISSEMINATION: Ethics approval is not required. Investigators will deidentify individual participant data before it is shared. The results will be submitted to a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42018090261.

Early hyperbaric oxygen therapy is associated with favorable outcome in patients with iatrogenic cerebral arterial gas embolism: systematic review and individual patient data meta-analysis of observational studies.

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) caused by invasive medical procedures may be treated with hyperbaric oxygen therapy (HBOT). Previous studies suggested that initiation of HBOT within 6-8 h is associated with higher probability of favorable outcome, when compared to time-to-HBOT beyond 8 h. We performed a group level and individual patient level meta-analysis of observational studies, to evaluate the relationship between time-to-HBOT and outcome after iatrogenic CAGE. METHODS: We systematically searched for studies reporting on time-to-HBOT and outcome in patients with iatrogenic CAGE. On group level, we meta-analyzed the differences between median time-to-HBOT in patients with favorable versus unfavorable outcome. On individual patient level, we analyzed the relationship between time-to-HBOT and probability of favorable outcome in a generalized linear mixed effects model. RESULTS: Group level meta-analysis (ten studies, 263 patients) shows that patients with favorable outcome were treated with HBOT 2.4 h (95% CI 0.6-9.7) earlier than patients with unfavorable outcome. The generalized linear mixed effects model (eight studies, 126 patients) shows a significant relationship between time-to-HBOT and probability of favorable outcome (p = 0.013) that remains significant after correcting for severity of manifestations (p = 0.041). Probability of favorable outcome decreases from approximately 65% when HBOT is started immediately, to 30% when HBOT is delayed for 15 h. CONCLUSIONS: Increased time-to-HBOT is associated with decreased probability of favorable outcome in iatrogenic CAGE. This suggests that early initiation of HBOT in iatrogenic CAGE is of vital importance.

Exceptional survival of an airplane stowaway, treated successfully with hyperbaric oxygen.

Survival of airplane stowaways is rare. Here we report an exceptional case of successful treatment and full recovery. After a transcontinental flight an unconscious stowaway was discovered in a wheel well of a Boeing 747-400F. Airport paramedics confirmed regular respiration and achieved 100% oxygen saturation (pulse oximetry) by high-flow oxygen. Rectal body temperature was 35.5 °C. On arrival at the emergency department, the patient's vital signs were stable. He did not respond to verbal stimuli. He localized to painful stimuli with both arms, however, there was no reaction to stimuli to both legs. We suspected his neurological deficits were caused by posthypoxic encephalopathy or altitude decompression sickness (DCS), the latter amenable to hyperbaric oxygen therapy (HBOT). HBOT was performed for 5 h (US Navy Treatment Table 6) and afterwards, full neurological recovery was documented. About 24 h after admission a new proximal paresis of the left leg was noted. Assuming recurrence of DCS, daily HBOT was scheduled for three days, after which motor function had again returned to normal. Stowaways travelling in airplane wheel wells experience extreme environmental circumstances. The presented patient survived an eight-hour exposure to calculated barometric pressures as low as 190 mmHg and ambient PO2 of 40 mmHg. Apart from creating awareness of this rare patient category, we want to stress the risk of altitude DCS in unpressurized flights. When DCS is suspected, immediate high-flow oxygen therapy should be initiated, followed by HBOT at the earliest opportunity.

The Effect of Hyperbaric Oxygen Therapy on Markers of Oxidative Stress and the Immune Response in Healthy Volunteers.

Hyperbaric oxygen therapy (HBOT) consists of breathing 100% oxygen under increased ambient pressure. There are indications that HBOT induces oxidative stress and activates immune pathways. However, previous research on immunological effects of HBOT has mainly been established in in vitro experiments and selected patient populations, limiting generalizability and increasing the chances of confounding by comorbidities and specific patient-related factors. More insight into the immunological effects of HBOT would aid investigation and comprehension of potentially novel treatment applications. Therefore, in this study, we investigated the effects of three 110-min HBOT-sessions with 24-h intervals on immunological parameters in healthy, young, male volunteers. Blood samples were obtained before and after the first and third HBOT sessions. We assessed neutrophilic reactive oxygen species (ROS) production, systemic oxidative stress [plasma malondialdehyde (MDA) concentrations] as well as neutrophil phagocytic activity, plasma concentrations of tumor necrosis factor (TNF), interleukin (IL)-6, IL-8, and IL-10, and production of TNF, IL-6, and IL-10 by leukocytes ex vivo stimulated with the Toll-like receptor (TLR) ligands lipopolysaccharide (TLR4) and Pam3Cys (TLR2). We observed decreased neutrophilic ROS production and phagocytosis following the second HBOT session, which persisted after the third session, but no alterations in MDA concentrations. Furthermore, plasma concentrations of the investigated cytokines were unaltered at all-time points, and ex vivo cytokine production was largely unaltered over time as well. These results indicate no induction of systemic oxidative stress or a systemic inflammatory response after repeated HBOT in healthy volunteers but may suggest exhaustion of ROS generation capacity and phagocytosis.

The Effects of Hyperbaric Oxygenation on Oxidative Stress, Inflammation and Angiogenesis.

Hyperbaric oxygen therapy (HBOT) is commonly used as treatment in several diseases, such as non-healing chronic wounds, late radiation injuries and carbon monoxide poisoning. Ongoing research into HBOT has shown that preconditioning for surgery is a potential new treatment application, which may reduce complication rates and hospital stay. In this review, the effect of HBOT on oxidative stress, inflammation and angiogenesis is investigated to better understand the potential mechanisms underlying preconditioning for surgery using HBOT. A systematic search was conducted to retrieve studies measuring markers of oxidative stress, inflammation, or angiogenesis in humans. Analysis of the included studies showed that HBOT-induced oxidative stress reduces the concentrations of pro-inflammatory acute phase proteins, interleukins and cytokines and increases growth factors and other pro-angiogenesis cytokines. Several articles only noted this surge after the first HBOT session or for a short duration after each session. The anti-inflammatory status following HBOT may be mediated by hyperoxia interfering with NF-κB and IκBα. Further research into the effect of HBOT on inflammation and angiogenesis is needed to determine the implications of these findings for clinical practice.

The Circulatory Effects of Increased Hydrostatic Pressure Due to Immersion and Submersion.

Increased hydrostatic pressure as experienced during immersion and submersion has effects on the circulation. The main effect is counteracting of gravity by buoyancy, which results in reduced extravasation of fluid. Immersion in a cold liquid leads to peripheral vasoconstriction, which centralizes the circulation. Additionally, a pressure difference usually exists between the lungs and the rest of the body, promoting pulmonary edema. However, hydrostatic pressure does not exert an external compressing force that counteracts extravasation, since the increased pressure is transmitted equally throughout all tissues immersed at the same level. Moreover, the vertical gradient of hydrostatic pressure down an immersed body part does not act as a resistance to blood flow. The occurrence of cardiovascular collapse when an immersed person is rescued from the water is not explained by removal of hydrostatic squeeze, but by sudden reinstitution of the effect of gravity in a cold and vasoplegic subject.

Seizures in Iatrogenic Cerebral Arterial Gas Embolism.

OBJECTIVES: Iatrogenic cerebral arterial gas embolism occurs when gas enters the cerebral arterial circulation during a medical procedure and is considered a severe complication. Seizures have been described in these patients, but information on clinical characteristics, treatment, and outcome is lacking in current literature. The aim of the study was to explore seizures in patients with iatrogenic cerebral arterial gas embolism and to evaluate management strategies. DESIGN: Retrospective single-center observational study. SETTING: The only university hospital in the Netherlands with a hyperbaric oxygen therapy facility. PATIENTS: All patients presenting at or referred to our center with iatrogenic cerebral arterial gas embolism between May 2016 and December 2020. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Fifteen patients with iatrogenic cerebral arterial gas embolism were identified, of whom 11 (73%) developed seizures. Five patients developed their first seizure prior to hyperbaric oxygen therapy, three during hyperbaric oxygen therapy, and three after hyperbaric oxygen therapy. Of the 11 patients with seizures, all but one were treated with anti-epileptic drugs. With a median follow-up time of 5 months (range, 1-54 mo), five patients showed complete neurologic recovery, five had minor neurologic deficit, two had moderate to severe neurologic deficit, and three had died. Four patients still used anti-epileptic drugs at follow-up. No patients had recurrent seizures after hospital discharge. CONCLUSIONS: `Seizures are a common symptom in iatrogenic cerebral arterial gas embolism. They are often treated with anti-epileptic drugs and do not seem to lead to chronic epilepsy.

Second Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

The COVID-19 pandemic poses great challenges for healthcare workers around the world, including perioperative specialists. Previously, we provided a first overview of available literature on SARS-CoV-2 and COVID-19, relevant for anaesthetists and intensivists. In the current review, we provide an update of this topic, after a literature search current through May 2020. We discuss the evidence on perioperative risk for COVID-19 patients presenting for surgery, the risk of transmission of SARS-CoV-2 in the operating room, and the current literature on laboratory diagnostics. Furthermore, cardiovascular and nervous system involvement in COVID-19 are discussed, as well as considerations in diabetic patients. Lastly, the latest evidence on pharmacological treatment is summarised.

Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management.

When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.

Perioperative Hyperoxyphobia: Justified or Not? Benefits and Harms of Hyperoxia during Surgery.

The use of an inspiratory oxygen fraction of 0.80 during surgery is a topic of ongoing debate. Opponents claim that increased oxidative stress, atelectasis, and impaired oxygen delivery due to hyperoxic vasoconstriction are detrimental. Proponents point to the beneficial effects on the incidence of surgical site infections and postoperative nausea and vomiting. Also, hyperoxygenation is thought to extend the safety margin in case of acute intraoperative emergencies. This review provides a comprehensive risk-benefit analysis for the use of perioperative hyperoxia in noncritically ill adults based on clinical evidence and supported by physiological deduction where needed. Data from the field of hyperbaric medicine, as a model of extreme hyperoxygenation, are extrapolated to the perioperative setting. We ultimately conclude that current evidence is in favour of hyperoxia in noncritically ill intubated adult surgical patients.

A retrospective cohort study of lidocaine in divers with neurological decompression illness.

Lidocaine is the most extensively studied substance for adjuvant therapy in neurological decompression illness (DCI), but results have been conflicting. In this retrospective cohort study, we compared 14 patients who received adjuvant intravenous lidocaine for neurological decompression sickness and cerebral arterial gas embolism between 2001 and 2011 against 21 patients who were treated between 1996 and 2001 and did not receive lidocaine. All patients were treated with hyperbaric oxygen (HBO2) therapy according to accepted guidelines. Groups were comparable for all investigated confounding factors, except that significantly more control patients had made an unsafe dive (62% vs. 14%, p = 0.007). Groups had comparable injury severity as measured by Dick and Massey score (lidocaine 2.7 +/- 1.7, control 2.0 +/- 1.6), an adapted version of the Dick and Massey score, and the Blatteau score. Number of HBO2 sessions given was comparable in both groups (lidocaine 2.7 +/- 2.3, control 2.0 +/- 1.0). There was neither a positive nor a negative effect of lidocaine on outcome (relative risk for objective neurological signs at follow-up in the lidocaine group was 1.8, 95% CI 0.2-16). This is the first retrospective cohort study of lidocaine in neurological DCI. Since our study is under-powered to draw definitive conclusions, a prospective multicenter study remains the only way to reliably determine the effect of lidocaine in neurological decompression illness.

Hyperbaric oxygen does not improve cerebral function when started 2 or 4 hours after cerebral arterial gas embolism in swine.

OBJECTIVE: Hyperbaric oxygenation is the accepted treatment for cerebral arterial gas embolism. Although earlier start of hyperbaric oxygenation is associated with better outcome, it is unknown how much delay can be tolerated before start of hyperbaric oxygenation. This study investigates the effect of hyperbaric oxygenation on cerebral function in swine when initiated 2 or 4 hours after cerebral arterial gas embolism. DESIGN: Prospective interventional animal study. SETTING: Surgical laboratory and hyperbaric chamber. SUBJECTS: Twenty-two Landrace pigs. INTERVENTIONS: Under general anesthesia, probes to measure intracranial pressure, brain oxygen tension (PbtO2), and brain microdialysis, and electrodes for electroencephalography were placed. The electroencephalogram (quantified using temporal brain symmetry index) was suppressed during 1 hour by repeated injection of air boluses through a catheter placed in the right ascending pharyngeal artery. Hyperbaric oxygenation was administered using U.S. Navy Treatment Table 6 after 2- or 4-hour delay. Control animals were maintained on an inspiratory oxygen fraction of 0.4. MEASUREMENTS AND MAIN RESULTS: Intracranial pressure increased to a mean maximum of 19 mm Hg (SD, 4.5 mm Hg) due to the embolization procedure. Hyperbaric oxygenation significantly increased PbtO2 in both groups treated with hyperbaric oxygenation (mean maximum PbtO2, 390 torr; SD, 177 torr). There were no significant differences between groups with regard to temporal brain symmetry index (control vs 2-hr delay, p = 0.078; control vs 4-hr delay, p = 0.150), intracranial pressure, and microdialysis values. CONCLUSIONS: We did not observe an effect of hyperbaric oxygenation on cerebral function after a delay of 2 or 4 hours. The injury caused in our model could be too severe for a single session of hyperbaric oxygenation to be effective. Our study should not change current hyperbaric oxygenation strategies for cerebral arterial gas embolism, but further research is necessary to elucidate our results. Whether less severe injury benefits from hyperbaric oxygenation should be investigated in models using smaller amounts of air and clinical outcome measures.