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Association between Intraoperative Hypotension and Postoperative Delirium

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Authors: Shiri Zarour, M.D. et al 
Anesthesiology October 2024, Vol. 141, 707–718.
Background

Intraoperative hypotension might contribute to the development of postoperative delirium through inadequate cerebral perfusion. However, evidence regarding the association between intraoperative hypotension and postoperative delirium is equivocal. Therefore, the hypothesis that intraoperative hypotension is associated with postoperative delirium in patients older than 70 yr having elective noncardiac surgery was tested .

Methods

This was a retrospective cohort analysis of patients older than 70 yr who underwent elective noncardiac surgery in a single tertiary academic center between 2020 and 2021. Intraoperative hypotension was quantified as the area under a mean arterial pressure (MAP) threshold of 65 mmHg. Postoperative delirium was defined as a collapsed composite outcome including a positive 4 A’s test during the initial 2 postoperative days, and/or delirium identification using the Chart-based Delirium Identification Instrument. The association between hypotension and postoperative delirium was assessed using multivariable logistic regression, adjusting for potential confounding variables. Several sensitivity analyses were performed using similar regression models.

Results

In total, 2,352 patients were included (median age, 76 yr; 1,112 [47%] women; 1,166 [50%] American Society of Anesthesiologists Physical Status III or greater; 698 [31%] having high-risk surgeries). The median [interquartile range] intraoperative area under the curve below a threshold of MAP less than 65 mmHg was 28 [0, 103] mmHg · min. The overall incidence of postoperative delirium was 14% (327 of 2,352). After adjustment for potential confounding variables, hypotension was not associated with postoperative delirium. Compared to the first quartile of area under the curve below a threshold of MAP less than 65 mmHg, patients in the second, third, and fourth quartiles did not have more postoperative delirium, with adjusted odds ratios of 0.94 (95% CI, 0.64 to 1.36; P = 0.73), 0.95 (95% CI, 0.66 to 1.36; P = 0.78), and 0.95 (95% CI, 0.65 to 1.36; P = 0.78), respectively. Intraoperative hypotension was also not associated with postoperative delirium in any of the sensitivity and subgroup analyses performed.

Conclusions

To the extent of hypotension observed in our cohort, our results suggest that intraoperative hypotension is not associated with postoperative delirium in elderly patients having elective noncardiac surgery.

Editor’s Perspective
What We Already Know about This Topic
  • It is plausible that intraoperative hypotension might contribute to the development of postoperative delirium through inadequate cerebral perfusion
  • Evidence regarding the association between intraoperative hypotension and postoperative delirium is equivocal, with some studies finding an association and others contradicting this conclusion
What This Article Tells Us That Is New
  • In this retrospective, single-center analysis of 2,352 patients older than 70 yr who underwent elective noncardiac surgery, the association between hypotension and postoperative delirium was assessed using multivariable logistic regression
  • In this cohort, characterized by relatively small “amounts” of hypotension as expressed by the relatively low area under the mean arterial pressure threshold of 65 mmHg and meticulous outcome acquisition, the results suggest that intraoperative hypotension is not associated with postoperative delirium in elderly patients having elective noncardiac surgery

Intraoperative Ventilation/Perfusion Mismatch and Postoperative Pulmonary Complications after Major Noncardiac Surgery

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Authors: Gaetano Scaramuzzo, M.D. et al 
Anesthesiology October 2024, Vol. 141, 693–706.
Background

Postoperative pulmonary complications can increase hospital length of stay, postoperative morbidity, and mortality. Although many factors can increase the risk of postoperative pulmonary complications, it is not known whether intraoperative ventilation/perfusion (V/Q) mismatch can be associated with an increased risk of postoperative pulmonary complications after major noncardiac surgery.

Methods

This study enrolled patients undergoing general anesthesia for noncardiac surgery and evaluated intraoperative V/Q distribution using the automatic lung parameter estimator technique. The assessment was done after anesthesia induction, after 1 h from surgery start, and at the end of surgery. Demographic and procedural information were collected, and intraoperative ventilatory and hemodynamic parameters were measured at each timepoint. Patients were followed up for 7 days after surgery and assessed daily for postoperative pulmonary complication occurrence.

Results

The study enrolled 101 patients with a median age of 71 [62 to 77] years, a body mass index of 25 [22.4 to 27.9] kg/m2, and a preoperative Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score of 41 [34 to 47]. Of these patients, 29 (29%) developed postoperative pulmonary complications, mainly acute respiratory failure (23%) and pleural effusion (11%). Patients with and without postoperative pulmonary complications did not differ in levels of shunt at T1 (postoperative pulmonary complications: 22.4% [10.4 to 35.9%] vs. no postoperative pulmonary complications:19.3% [9.4 to 24.1%]; P = 0.18) or during the protocol, whereas significantly different levels of high V/Q ratio were found during surgery (postoperative pulmonary complications: 13 [11 to 15] mmHg vs. no postoperative pulmonary complications: 10 [8 to 13.5] mmHg; P = 0.007) and before extubation (postoperative pulmonary complications: 13 [11 to 14] mmHg vs. no postoperative pulmonary complications: 10 [8 to 12] mmHg; P = 0.006). After adjusting for age, ARISCAT, body mass index, smoking, fluid balance, anesthesia type, laparoscopic procedure and surgery duration, high V/Q ratio before extubation was independently associated with the development of postoperative pulmonary complications (odds ratio, 1.147; 95% CI, 1.021 to 1.289; P = 0.02). The sensitivity analysis showed an E-value of 1.35 (CI, 1.11).

Conclusions

In patients with intermediate or high risk of postoperative pulmonary complications undergoing major noncardiac surgery, intraoperative V/Q mismatch is associated with the development of postoperative pulmonary complications. Increased high V/Q ratio before extubation is independently associated with the occurrence of postoperative pulmonary complications in the first 7 days after surgery.

Editor’s Perspective
What We Already Know about This Topic
  • Intraoperative physiologic parameters implicated in the development of postoperative pulmonary complications have not been well elucidated
  • Ventilation/perfusion mismatch is implicated, but direct measurement is complex and difficult to do in noncardiac surgery
  • Automatic lung parameter estimation is an alternative technique to the more complex multiple inert gas elimination technique
What This Article Tells Us That Is New
  • Using automatic lung parameter estimation, the authors assessed ventilation/perfusion matching at three time periods in intubated patients undergoing noncardiac surgery at high or intermediate risk for postoperative pulmonary complications
  • After multivariable adjustment, high ventilation/perfusion ratio just before extubation was independently associated with postoperative pulmonary complications within 7 days of surgery

A Great Anesthesiologist Opportunity in Gadsden AL

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We are seeking a dedicated anesthesia care team to join our new anesthesia care team contract at Riverview Regional Medical Center.  Gadsden is a town of over 100,000 people that is located 1 hour from Birmingham AL and 2 hours from Atlanta GA.

Position Highlights:

  • Anesthesiologist call is 1:3
  • Competitive salary of $500,000 plus benefits.
  • 8 weeks of vacation.

Interested? Please contact me at 660-596-2224 or drrob@anesthesiaexperts.com if you or anyone you know would like to apply.

Note: Agencies, please do not contact us as we do not use your service

Discover The Best Anesthesiologist Opportunity in New Mexico

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We are seeking a dedicated anesthesiologist to join our all-anesthesiologist group. Our team will consist of 4 full-time providers and 1 for vacation relief, managing 3 operating rooms.

Position Highlights:

  • Zero call for 3 weeks, followed by 1 week of call without daytime work only call after 7 PM therefore you may not work the entire week.
  • Competitive salary of $500,000 plus benefits.
  • 8 weeks of vacation.

This is the best job on GasWork #370670

Interested? Please contact me at 660-596-2224 or drrob@anesthesiaexperts.com if you or anyone you know would like to apply.

Note: Agencies, please do not contact us as we do not use your service

Manual vs. End-Tidal Inhalational Anesthesia

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Radius Anesthesia

The delivery of anesthesia during surgical procedures can be managed by manual control or automated end-tidal control, each of which has distinct advantages and disadvantages. Manual control of anesthesia involves the anesthesiologist directly adjusting the delivery of anesthetic gases based on the patient’s physiologic state as measured by ongoing assessment. In contrast, end-tidal control uses automated systems to regulate the concentration of anesthetic gases by measuring the concentration of gases exhaled by the patient, providing a feedback loop that continuously adjusts the delivery to maintain a set value.

Manual control relies heavily on the anesthesiologist’s expertise and ability to anticipate and respond to changes in the patient’s condition. It allows for tailored adjustments based on clinical judgment, which can be beneficial in complex or rapidly changing scenarios. However, this approach can be labor intensive and can lead to variability in depth of anesthesia, potentially increasing the risk of intraoperative awareness or excessive anesthesia. Studies have shown that manual adjustments can lead to fluctuations in anesthetic concentration and gas consumption, which can affect the stability and efficiency of the anesthesia delivery process (Swami et al., 2020).

End-tidal control systems, such as those using target-controlled infusion algorithms, automate the delivery of anesthesia by continuously adjusting fresh gas flow and vaporizer output to maintain a target end-tidal concentration, though the anesthesiologist decides on certain settings, monitors the patient, and can takeover manual control as needed. This automation can increase the precision of anesthetic delivery, reduce anesthesiologist workload, and minimize anesthetic gas consumption, providing both clinical and economic benefits. According to Skalec et al. (2019), automated end-tidal control significantly reduces anesthetic gas consumption and improves anesthetic depth stability compared to manual control. This efficiency may also translate into environmental benefits by reducing the emission of anesthetic gases, which are known to contribute to air pollution.

In terms of patient outcomes, the use of end-tidal control has been associated with improved hemodynamic stability and reduced intraoperative variability in depth of anesthesia compared to manual control. A randomized controlled trial comparing manual and automated control during open-heart surgery found that the use of closed-loop end-tidal control systems significantly improved the precision of anesthesia delivery, resulting in more stable hemodynamic parameters (Madhavan et al., 2011). This precision not only improves patient safety, but also reduces the likelihood of complications associated with over- or under-dosing of anesthetic agents.

Despite the benefits of end-tidal control, it is not without limitations. Automated systems may lack the nuanced adjustments that a skilled anesthesiologist can make in response to unique or unexpected clinical situations. There is also a reliance on the accuracy of the sensors and algorithms used in these systems, which can occasionally malfunction or provide erroneous data. As noted by Arora et al. (2020), while end-tidal control systems generally outperform manual adjustments in stable, predictable scenarios, their effectiveness may be reduced in cases of equipment failure or when managing patients with atypical respiratory physiology.

Overall, both manual and end-tidal control methods have their place in anesthesia management. The choice between the two may depend on the specific clinical context, the complexity of the surgery, and the experience of the anesthesia team. Future advances in technology and further refinement of automated systems may further enhance the capabilities of end-tidal control, potentially making it the preferred method in a wider range of surgical settings.

References

  1. Swami A, Arora K, Puppala P. Comparative study of automated end-tidal control versus manual fresh gas flow adjustment with respect to gas usage and delivery during low-flow anesthesia. Anesthesia and Critical Care. 2020.
  2. Skalec T, Górecka-Dolny A, Zieliński S, et al. Comparison of anaesthetic gas consumption and stability of anaesthesia using automatic and manual control over the course of anaesthesia. Anestezjologia. 2019.
  3. Madhavan JS, Puri GD, Mathew PJ. Closed-loop isoflurane administration with bispectral index in open heart surgery: randomized controlled trial with manual control. Acta Anaesthesiologica Taiwanica. 2011.
  4. Arora K, Swami A, Puppala P, Rai A. Comparative study of automated end tidal control versus manual fresh gas flow adjustment with respect to gas usage and delivery during low flow anesthesia. Anesthesia and Critical Care. 2020.

Bioequivalence and pharmacokinetics of intravenous calcium during cesarean delivery

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Authors: Jessica R. Ansari, MD, MS et al 
Anesthesiology Newly Published on October 2024.
Background

Few studies have assessed the dose ratio of calcium gluconate to calcium chloride or defined the time course of change in serum ionized calcium concentration after intravenous injection.

Methods

In a bioequivalence (dose ratio) trial, parturients undergoing cesarean delivery were randomly assigned to receive calcium chloride 0.5 grams or calcium gluconate 1.5 or 2 grams by 10-minute intravenous infusion. Venous serum ionized calcium concentration was measured prior to calcium infusion and approximately 5, 10, 15, 30, and 60 minutes after infusion start. We combined these data with serum ionized calcium concentration measurements in parturients who received 1 gram calcium chloride or saline placebo in two recent clinical trials to define the pharmacokinetics of intravenous calcium over the first hour during and after drug administration.

Results

The bioequivalence study enrolled 34 participants, from whom we collected 181 serum ionized calcium concentration measurements. The dose ratio of calcium gluconate to calcium chloride was 3.11 (95% CI: 2.77-3.48). Population pharmacokinetics of calcium were determined using 311 serum ionized calcium concentration measurements from 70 parturients. The pharmacokinetics of intravenous calcium were described by a two-compartment model with systemic clearance of 0.18 (95% CI: 0.07–0.27) L/min, distributional clearance of 1.25 (95%CI: 1.03–1.56) L/min, central volume of 10.9 (95% CI: 9.3–12.6) L, and peripheral volume of 16.5 (95% CI: 12.5–24.7) L. After adjusting for the dose ratio, calcium gluconate and calcium chloride had identical time courses. A one-gram infusion of calcium chloride results in a peak increase in serum ionized calcium concentration of 0.39 (0.38-0.42 mmol/L), which decreases by half 29 (23-40) minutes after initiation of the 10-minute infusion.

Conclusions

We confirmed a 3:1 dose ratio of calcium gluconate to calcium chloride and estimated the pharmacokinetics over the first hour following intravenous delivery. These data inform clinical care and may guide future trials assessing calcium efficacy to reduce bleeding in obstetric patients.

Analgesic Effect of Exercise on Neuropathic Pain via Regulating the Complement Component 3 of Reactive Astrocytes

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AUTHORS: Wang, Chenghao PhD et al 

Anesthesia & Analgesia 139(4):p 840-850, October 2024.

BACKGROUND:

Exercise has been proven to be an efficient intervention in attenuating neuropathic pain. However, the underlying mechanisms that drive exercise analgesia remain unknown. In this study, we aimed to examine the role of complement component 3 (C3) in neuropathic pain and whether antinociceptive effects are produced by exercise via regulating C3 in mice.

METHODS:

In this study, using a spared nerve injury (SNI)-induced neuropathic pain mice model, C57BL/6J mice were divided into 3 groups: Sham mice, SNI mice, and SNI + Exercise (Ex) mice with 30-minute low-intensity aerobic treadmill running (10 m/min, no inclination). Paw withdrawal threshold; thermal withdrawal latency; and glial fibrillary acidic protein, C3, tumor necrosis factor-α, and interlukin-1β expression in the spinal cord were monitored. C3 knockout (KO) mice were further used to verify the role of C3 in neuropathic pain.

RESULTS:

von Frey test, acetone test, and CatWalk gait analysis revealed that treadmill exercise for 4 weeks reversed pain behaviors. In addition, exercise reduced astrocyte reactivity (SNI mean = 14.5, 95% confidence interval [CI], 12.7–16.3; SNI + Ex mean = 10.3, 95% CI, 8.77–11.9, P = .0003 SNI + Ex versus SNI) and inflammatory responses in the spinal cord after SNI. Moreover, it suppressed the SNI-induced upregulation of C3 expression in the spinal cord (SNI mean = 5.46, 95% CI, 3.39–7.53; SNI + Ex mean = 2.41, 95% CI, 1.42–3.41, P = .0054 SNI + Ex versus SNI in Western blot). C3 deficiency reduced SNI-induced pain and spinal astrocyte reactivity (wild type mean = 7.96, 95% CI, 6.80–9.13; C3 KO mean = 5.98, 95% CI, 5.14–6.82, P = .0052 C3 KO versus wild type). Intrathecal injection of recombinant C3 (rC3) was sufficient to produce mechanical (rC3-Ex mean = 0.77, 95% CI, 0.15–1.39; rC3 mean = 0.18, 95% CI, −0.04 to 0.41, P = .0168 rC3-Ex versus rC3) and cold (rC3-Ex mean = 1.08, 95% CI, 0.40–1.77; rC3 mean = 3.46, 95% CI, 1.45–5.47, P = .0025 rC3-Ex versus rC3) allodynia in mice. Importantly, exercise training relieved C3-induced mechanical and cold allodynia, and the analgesic effect of exercise was attenuated by a subeffective dose of intrathecal injection of C3.

CONCLUSIONS:

Overall, these results suggest that exercise suppresses neuropathic pain by regulating astroglial C3 expression and function, thereby providing a rationale for the analgesic effect of exercise as an acceptable alternative approach for treating neuropathic pain.

KEY POINTS

  • Question: What are the underlying mechanisms that drive exercise analgesia in neuropathic pain?
  • Findings: Exercise suppresses neuropathic pain by regulating astroglial component 3 (C3) expression and function.
  • Meaning: The study provides a rationale for the analgesic effect of exercise as an acceptable alternative approach for treating neuropathic pain.

Clinical Decision Support as a Prevention Tool for Medication Errors in the Operating Room

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AUTHORS: Amici, Lynda D. DNP, CRNA et al 

Anesthesia & Analgesia 139(4):p 832-839, October 2024.

BACKGROUND:

Medication errors in the operating room have high potential for patient harm. While electronic clinical decision support (CDS) software has been effective in preventing medication errors in many nonoperating room patient care areas, it is not yet widely used in operating rooms. The purpose of this study was to determine the percentage of self-reported intraoperative medication errors that could be prevented by CDS algorithms.

METHODS:

In this retrospective cross-sectional study, we obtained safety reports involving medication errors documented by anesthesia clinicians between August 2020 and August 2022 at a 1046-bed tertiary care academic medical center. Reviewers classified each medication error by its stage in the medication use process, error type, presence of an adverse medication event, and its associated severity and preventability by CDS. Informational gaps were corroborated by retrospective chart review and disagreements between reviewers were resolved by consensus. The primary outcome was the percentage of errors that were preventable by CDS. Secondary outcomes were preventability by CDS stratified by medication error type and severity.

RESULTS:

We received 127 safety reports involving 80 medication errors, and 76/80 (95%) of the errors were classified as preventable by CDS. Certain error types were more likely to be preventable by CDS than others (P < .001). The most likely error types to be preventable by CDS were wrong medication (N = 36, 100% rated as preventable), wrong dose (N = 30, 100% rated as preventable), and documentation errors (N = 3, 100% rated as preventable). The least likely error type to be preventable by CDS was inadvertent bolus (N = 3, none rated as preventable).

CONCLUSIONS:

Ninety-five percent of self-reported medication errors in the operating room were classified as preventable by CDS. Future research should include a randomized controlled trial to assess medication error rates and types with and without the use of CDS.

Characterizing Chronic Pain and Adverse Childhood Experiences in the Lesbian, Gay, Bisexual, Transgender, or Queer Community

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AUTHORS: Shirsat, Nikita BS et al 

Anesthesia & Analgesia 139(4):p 821-831, October 2024.

BACKGROUND:

Childhood adversity is associated with chronic pain in adulthood. Additionally, individuals identifying as lesbian, gay, bisexual, transgender, or queer (LGBTQ+) report a greater prevalence of chronic pain and increased adverse childhood experiences (ACEs). While the LGTBQ+ community has a disproportionately high chronic disease burden, limited research has been conducted on the associations between chronic pain conditions or intensity and childhood adversity in this population.

METHODS:

In this cross-sectional study, participants were 18 years or older, LGBTQ+ identifying, and reported chronic pain. Surveys were electronically distributed from August to November 2022 via LGBTQ+ organization email listservs and social media platforms. The survey included demographics and validated questionnaires measuring chronic pain (The Chronic Pain Questionnaire) and childhood adversity (ACE score). In analysis, ACE scores of 4 or more were defined as high.

RESULTS:

Responses from 136 individuals (average age of 29 ± 7.4 years) were analyzed. The mean for participants’ average pain rating in the last 6 months was 5.9 of 10. Participants’ worst pain was rated at least a 7 of 10 for 80% of respondents. Half (47%) had high ACE scores, and high ACE scores were significantly associated with higher average pain scores (6.27 ± 1.79, mean difference = −2.22, P = .028, 95% confidence interval [CI], –1.2 to −0.0), and higher perceived current pain ratings (4.53 ± 2.16, mean difference = −2.78, P = .007, 95% CI, –1.9 to −0.3). Transgender and gender diverse (TGD) participants (n = 75) had higher ACE scores (3.91 ± 1.78) and current pain scores compared to cisgender individuals (3.9 ± 1.8 vs 3.0 ± 1.9, P = .009, 95% CI, 0.0–0.3). History of any sexual trauma was prevalent in 36.7% and was associated with chronic pain located in the pelvic region (P = .016, effect size estimate 0.21). Specific histories of forced sexual and touch encounters were associated with a specific diagnosis of fibromyalgia (P = .008, effect size estimate 0.31 and P = .037, effect size estimate 0.31, respectively).

CONCLUSIONS:

Childhood adversity and chronic pain’s dose-dependent relationship among our LGBTQ+ sample indicates a need to explore trauma’s role in perceived pain. Given sexual trauma’s association with pain location and diagnosis, type of trauma may also be crucial in understanding chronic pain development. Research into the relationships between childhood adversity, sexuality, gender identity, and chronic pain could improve chronic pain prevention and management for the LGBTQ+ community.

End-Tidal Control Versus Manual Control of Inhalational Anesthesia Delivery

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AUTHORS: McCabe, Melissa D. MD, FASA, MSCR et al 

Anesthesia & Analgesia 139(4):p 812-820, October 2024.

BACKGROUND:

Precise anesthesia delivery helps ensure amnesia, analgesia, and immobility. Conventionally, the end-tidal anesthetic concentration is maintained through manual adjustment of the fresh gas flow and anesthetic vaporizer output. Some anesthesia delivery systems can deliver and maintain clinician-selected end-tidal anesthetic agent (EtAA) concentration using a modified closed-loop system. We evaluated the performance of an End-tidal Control (EtC) system on the Aisys CS2 anesthesia machine (GE HealthCare). We hypothesized EtC anesthetic delivery would be noninferior to manually controlled anesthetic delivery.

METHODS:

The Multi-site Anesthesia randomized controlled STudy of End-tidal control compared to conventional Results (MASTER) Trial evaluated anesthetic delivery in 210 adult patients receiving inhaled anesthesia. Patients were randomized to either EtC or manual control (MC) anesthetic delivery. The primary objective was to determine whether, compared to conventional anesthesia practice, EtC achieves and maintains clinician-specified EtAA and end-tidal oxygen (Eto2) concentrations within defined noninferiority limits. Noninferiority was concluded if the lower limit of the 95% confidence interval (CI) of the difference between the percent duration within the acceptable range (5% of steady state or a margin of ~10% of each agent’s minimum alveolar concentration) for EtC and MC was ≥ −5% for both EtAA and Eto2. Secondary objectives included performance measures: response time: time required to attain 90% of the first desired EtAA, overshoot: amount the controller (or vaporizer delivery) exceeded the desired EtAA, and accuracy: average deviation from the desired EtAA.

RESULTS:

EtC achieved and sustained targeted EtAA and Eto2 concentrations within the noninferiority threshold. The EtAA was within 5% of the desired value 98% ± 2.05% of the time with EtC compared to 45.7% ± 31.7% of the time with MC (difference 52.3% [95% CI, 45.9%–58.6%], P < .0001). For Eto2, EtC was within the noninferiority limit 86.3% ± 22.8% of the time compared with MC at 41% ± 33.3% (P < .0001, difference 45.3% [95% CI, 36.1%–54.5%]). The median response time for achieving 90% of the initial EtAA desired value was 75 seconds with EtC and 158 seconds with MC (P = .0013). EtC exhibited a median overshoot of 6.64% of the selected EtAA concentration, whereas MC often failed to reach the clinician’s desired value. The difference in median percent deviation from desired EtAA value was 15.7% ([95% CI, 13.5%–19.0%], P < 0001).

CONCLUSIONS:

EtC achieves and maintains the EtAA and Eto2 concentration in a manner that is noninferior to manually controlled anesthesia delivery.

KEY POINTS

Question: Can an end-tidal-controlled anesthesia delivery system achieve and maintain a desired anesthesia concentration?

Findings: The end-tidal-controlled anesthesia delivery system achieves and maintains a desired anesthetic concentration.

Meaning: End-tidal-controlled anesthesia delivery is a viable alternative to conventional, manually titrated anesthesia delivery.

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