OHSU Research Ideas

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Ideas

Good

• Does change in PPV/CO after SCD activation predict fluid responsiveness and how does it compare to SLR?
• Does sugammadex interfere with HRT in post-menopausal and/or lactating women? (0 articles mentioning both Sugammadex and Menopause)
• EEG/MEP/SSEP patterns in monkeys/humans taking THC vs controls
• Buprenorphine for induction or acute pain treatment in perioperative setting
• Surgical TAP block vs US guided
• Xenon recycling
• Yohimbine for precedex reversal
• Can ET O2 and FiO2 gradient be used to calculate VO2?
• Does setting realistic pain expectations in pre-op decrease self-reported pain scores in PACU?

Very Ambitious, But Still Cool

• NIBP monitoring from head/neck
• Can you modulate the strength of the Bohr effect to extract more hemoglobin from oxygen (thus prolonging apnea time before desaturation)? Humpback whales (and very small animals) have a much stronger Bohr effect, presumably from hemoglobin mutations. One approach would be non-immunogenic artificial hemoglobin proteins (made with CRISPR and perhaps packaged into empty RBCs?), another option would be some drug that modulates the Bohr effect on human Hgb.
• Better way of determining fluid status
• Novel reversal agents (e.g. volatile anesthetics, propofol, precedex)
• Permanently inhibit a nerve to prevent phantom pain after amputation.
• Reversible chemical/optical/electromagnetic knockdown/inhibition/interference of pain nuclei/DRG/dorsal column/STT activity in rodents/primates
• Fentanyl patch instead of remifentanil infusion? What other anesthetics could you deliver via patch? Could you do a patch induction for Peds? There is no remifentanil or sufentanil patch.
• Find a better trigger for transfusion threshold. Hgb mass loss vs. qBL vs. EBL are all various ways of getting at how much blood was lost, but why do we even care? Is that even useful information? How much Hgb do you need? Is Hgb concentration even the right thing to measure for a transfusion threshold? What you really want to know is whether they lost so much blood that they require a transfusion to provide adequate tissue oxygenation. Are there other reasons to care? Is there an early marker of tissue hypoxia that would make a better laboratory marker for determining need for blood transfusion?
  • Hgb mass loss (HML) takes the concentration of Hgb in the suction canister (including irrigation) and multiplies it by the volume to yield the total hemoglobin mass in the canister. This could then be divided by the starting Hgb concentration to determine the volume of blood lost.
  • Assuming the blood is lost acutely, there initially should be no change in the Hgb concentration. Over a sub-acute time frame two dilutional factors kick in, volume resuscitation with crystalloid and fluid shifts from the interstitial to the intravascular compartment.
  • Assuming 100% stayed intravascular and there were no fluid shifts between compartments to compensate, could you predict the new Hgb concentration after fluid administration based on how much volume was given? Probably not, given that you know C1 but not V1, and you are trying to solve for C2 but don't know V2. You do know the volume lost and the volume given back with concentration of 0, but I'm not sure if that is helpful. Assuming a standard blood volume based on patient averages may not be accurate because patients will come to surgery with unpredictable confounders like bleeding/dehydration. The starting blood volume could be measured (e.g. with nuclear medicine assay), but even then you won't know how much of the resuscitation fluid will stay intravascular or how much fluid is shifting between compartments. If you knew the starting blood volume, you could at least say what fraction of total Hgb was lost.

Already Done

• Wearable clinical alarms (2 relevant results, 1 highly relevant result)
• VR for IV placement peds (6 articles spanning 2020-2022, 5 RCTs, and a systematic-review and meta-analysis)
• Does precedex really delay emergence? (2022 Anesthesia and Analgesia Systematic Review and Meta-Analysis says "NO").

Not Super Exciting/Impactful

• Which findings on the preop note predict pressors use during the case?
• EPIC timeline builder
• Ultrasound vs blind A-line first attempt success rate and complications?
• How do epidurals affect gastric emptying in labor?

When did the ASA make their guideline for fasting? Which studies were cited? Which studies was the ASA (presumably) aware of? Ultimately, the clinical implications of answering this question would hinge on whether the results would change the ASA guidelines. If new information is unlikely to change guidance, then pursuing this question would be less relevant. Fasting for a few hours post-epidural is very low risk compared to the admittedly rare event of clinically significant aspiration. If you show that epidurals increase gastric emptying that would suggest that they also decrease risk of aspiration. However, if you then let patients with epidurals eat, they have a full stomach and their risk of aspiration is heightened despite any protective effect of an epidural. In other words, the lowest risk category of patients, assuming my hypothesis is true, remains fasted patients with epidurals.

Reference	Population	Intervention	Comparator	Outcome
Weiniger et al Eur J of Anaes 2022	80 non-fasted pregnant women, age 18+, GA 37+ weeks, singleton, cephalad, dilated <= 5 cm, 63 had empty stomachs and 17 had full stomachs at baseline	Double-blind single center RCT with women randomized to low-dose (50) or high-dose (100) epidural fentanyl.	Stomach antrum cross-sectional area (CSA) was measured with gastric US before and 2 hrs after fentanyl administration	No differences between low-dose and high-dose fentanyl groups.
Chassard et al Anes 2022	40 women	Prospective cohort study. Gastric ultrasound (gUS) was used to verify an empty stomach, then participants ate 125 g of yogurt within 5 min. For the epidural group, the meal was consumed within one hour of epidural placement.	10 parturients with labor epidural were compared with 10 pregnant women at term, 10 non-pregnant women, and 10 parturiants with no labor epidural. Serial gUS was performed at 15, 60, 90, and 120 minutes after a light meal and fraction of gastric emptying was calculated as [Area_Antral_90 / Area_Antral_15 - 1]*100.	Gastric emptying fraction (higher is better) was 52% (non-pregnant), 45% (pregnant), 7% (parturiants w/o epidural), and 31% (parturiants w/ epidural). Parturiants had delayed gastric emptying compared to non-parturiants, and epidural analgesia actually sped up gastric emptying.
Bonnet et al BJA 2014	60 spontaneously laboring parturients with ropivacaine/sufentanil PCEA analgesia	CSA measured with binary outcome of "full" or "not full" based on cutoff CSA value of >320 determined in small pilot study of 6 pregnant women.	gUS compared CSA when the anesthesiologist was called for epidural placement (beginning of labor) and at full cervical dilation.	50% had full stomachs at epidural placement compared to 13% at full cervical dilation.
Inada et al J of Anes 2009	16 ASA 1-2 term parturients undergoing elective cesarean delivery	CSE w/ 10 mg Bupivacaine and 10 mcg Fentanyl	Four channel electrogastrography was performed for 10 min at 5 interval time points.	Frequency of gastric contractions increased after spinal anesthetic, during the surgery, and returned to the (presumed) non-pregnant normal values by POD7.
Avram et al Anes and Analg 2007	10 obese (pre-pregnancy BMI > 35), pregnant, term, non-laboring, fasted women	gUS measurement of CSA and acetaminophen absorption test was used to measure gastric emptying	1.5g APAP was taken with 50 or 300 ml of water (cross-over design randomly assigned and separated by 2+ days) before measurement/calculation of CSA, gastric emptying half-time, APAP AUC, and C(max) T(max) for APAP concentration.	There were no differences in CSA, gastric 1/2 time, AUC, C(max), or T(max) between the 50 and 300 ml tests.
O'Sullivan et al Anes 1999	94 women in labor	Women were randomised to light diet or water only	CSA and metabolic profiles were compared, as well as length of labor and labor outcome	Blood glucose and insulin were higher and plasma betahydroxybutyrate and non-esterified fatty acids were lower in the diet group. There were no differences in labor course, labor outcomes (e.g. mode of delivery, umbilical artery/vein samples, and APGAR scores). CSA was higher in the diet group as was emesis volume.
Reynolds et al Anes 1997	56 women in labor, >36 weeks gestation, singleton, cephalad, no systemic opioids	Women had epidurals placed and were given 1.5g of paracetamol, then had serum levels measured at 0, 15, 30, 45, 60, and 90 minute timepoints.	Women were randomly assigned to either 0.125% bupivacaine solution or 0.0625% bupivacaine with 2.5 mcg/ml fentanyl, with continuous infusion rate titrated to effect. Rescue boluses of 5 ml 0.25% bupivacaine were given as needed. In study A, 28 women received paracetamol after 30 ml (75 mcg of fentanyl), while in study B it was after 40-50 ml (100-125 mcg of fentanyl).	No significant differences in AUC, peak concentration, or time to peak concentration in study A. In study B, the time to max concentration was delayed in the fentanyl group.
Mirakhur et al Anes and Analg 1997	105 parturiants	APAP absorption assay was done in women getting neuraxial labor analgesia	Neuraxial analgesia was administered with bupivacaine and 25 mcg intrathecal fentanyl (S), 50 mcg epidural fentanyl (E), or no opioid (C). APAP CMax, TMax, and AUC were measured at 60 and 120 min	Median (range) TMax values were 120 (15-180), 82.5 (15-180), and 90 (15-180) min in Groups S, E, and C, respectively (P < 0.05). Mean ± SD CMax was 13.4 ± 8.82, 17.9 ± 8.06, and 15.0 ± 6.22 µg/mL in Groups S, E, and C, respectively (P < 0.05). Mean ± SD AUC90 and AUC120 were also significantly smaller in Group S than in the other two groups (430 ± 616, 736 ± 504, and 672 ± 453; and 649 ± 592, 1063 ± 627, and 1053 ± 616 µg/ml/min in Groups S, E, and C, respectively).

Resources

• Schnell lab
• Leimer/Lo lab (THC, NHPs)
• Saugstad lab (EVs)
• Schennings (Gas vs. TIVA risk of post-op delirium, assessed via CAM)
• Schulman (interrogate ICDs for EMI after surgery)
• Austin Peters
• Selva Balkan
• Dale Hodges
• Liz Moss
• Jeff Davis
• Brandon Togioka

SCD hemodynamic effects

Caption text

Reference	Population	Intervention	Comparator	Outcome
Moady et al IMAJ 2019	Healthy volunteers and HFrEF patients	Pneumatic sleeve (PS) compression devices applied to both legs from toe to thigh and inflated to a pressure of 50 or 80 mmHg. the same method does not exacerbate symptoms and increases CO via an increase in SV, decreases SVR, and has no effect on HR (see ref 17).	Example	In healthy volunteers, there was increased CO, decrease SVR, and have no effect on HR (see ref 16). HFrEF patients who were medically optimized had no change in any hemodynamic parameter after 60 minutes of PS application, and that they tolerated it well without any increase in their BNP.
Bickel et al J of Card Failure 2014	Patients with HFrEF (mean LVEF 30%)	ISPC devices applied to both legs and cycled every 2 min for 40 min.	Example	Increased CO, SV, and decreased SVR w/o any effect on HR and without causing signs or symptoms of heart failure exacerbation. CVP and atrial size increased during ISPC activation.
Gibbons et al Experimental Physiology 2019	14 healthy university students	Four 3 minute trials of orthostatic maneuvers (stand-to-squat or thigh cuff compression/release) were done in random order with half of the trials involving ISPC (5 cuffs, peristaltic motion, applied over 200 ms, 65 mmHg, timed to local diastolic phase) of the lower extremity timed to counteract orthostatic changes (return to standing or after thigh-cuff release). Hemodynamic parameters (superficial femoral artery, MAP, Doppler ultrasound cardiac output, total peripheral resistance, middle cerebral artery blood velocity (MCAv), and cerebral tissue saturation index) were measured non-invasively before, during, and after	Example	Decreased TPR, heart rate; increased CO (via increased SV), TSI, and MCAv
Helmi et al Future Cardiology 2013	Example	Example	Example	Example
Kiefer et al Anesthesiology 2011	Example	Example	Example	Example
Kwak et al J of Neurosurgical Anesthesiology 2011	Example	Example	Example	Example
Kwak et al Arthroscopy 2010	Example	Example	Example	Example
Fanelli et al J of Clin Anesthesia 2008	Example	Example	Example	Example
Sohn et al Circulation J 2008	Example	Example	Example	Example