Jason M. Johanning

Postoperative Delirium in Older Adults: Best Practice Statement from the American Geriatrics Society

Disclosure Information: Disclosures for the members of t Geriatrics Society Postoperative Delirium Panel are listed in Support: Supported by a grant from the John A Hartford Fou to the Geriatrics-for-Specialists Initiative of the American Geri (grant 2009-0079). This article is a supplement to the American Geriatrics Soci Practice Guidelines for Postoperative Delirium in Older Adu at the American College of Surgeons 100 Annual Clinic San Francisco, CA, October 2014.

American Geriatrics Society abstracted clinical practice guideline for postoperative delirium in older adults

The abstracted set of recommendations presented here provides essential guidance both on the prevention of postoperative delirium in older patients at risk of delirium and on the treatment of older surgical patients with delirium, and is based on the 2014 American Geriatrics Society (AGS) Guideline. The full version of the guideline, American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults is available at the website of the AGS. The overall aims of the study were twofold: first, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the prevention of postoperative delirium in older adults; and second, to present nonpharmacologic and pharmacologic interventions that should be implemented perioperatively for the treatment of postoperative delirium in older adults. Prevention recommendations focused on primary prevention (i.e., preventing delirium before it occurs) in patients who are at risk for postoperative delirium (e.g., those identified as moderate‐to‐high risk based on previous risk stratification models such as the National Institute for Health and Care Excellence (NICE) guidelines, Delirium: Diagnosis, Prevention and Management. Clinical Guideline 103; London (UK): 2010 July 29). For management of delirium, the goals of this guideline are to decrease delirium severity and duration, ensure patient safety and improve outcomes.

Inhibition of reactive oxygen species attenuates aneurysm formation in a murine model

Reactive oxygen species (ROS) are increased in human abdominal aortic aneurysms (AAA). NADPH oxidases are the predominant source of superoxide anion (O(2)(-)) in the vasculature. Inducible nitric oxide synthase (iNOS) produces a significant amount of nitric oxide (NO) during inflammatory processes. We hypothesized that ROS produced by NADPH oxidases and iNOS played an important role in aneurysm formation. We examined this hypothesis using selective blockade of NADPH oxidases and iNOS in a murine model of AAA. Mice, including C57BL/6, iNOS knockout (iNOS(-/-)) mice, and its background matched control (C57BL/6), underwent AAA induction by periaortic application of CaCl(2). Aortic diameter was measured at aneurysm induction and harvest. Beginning 1 week prior to aneurysm induction and continuing to aortic harvest 6 weeks later, one group of the C57BL/6 mice were treated with orally administered apocynin (NADPH oxidase inhibitor). Control mice were given water. The mean diameter and change in diameter of each group were compared with concurrent controls. Aortic levels of the NO metabolite, NO(x) (NO(2) and NO(3)), were significantly increased in CaCl(2)-treated wild type mice. INOS(-/-) mice were partly resistant to aneurysm induction. This was associated with reduced expression of matrix metalloproteinase (MMP)-2 and MMP-9 and decreased production of NO(x) in the aortic tissues. Inhibition of NADPH oxidase by apocynin also blocked aneurysm formation. In conclusion, both iNOS deficiency and NADPH oxidase inhibition suppressed aneurysm formation in association with decreased NO(x) levels. These studies suggest that both NADPH oxidase and iNOS pathways contribute to ROS production and AAA development.

Claudication distances and the Walking Impairment Questionnaire best describe the ambulatory limitations in patients with symptomatic peripheral arterial disease

BACKGROUND Claudication secondary to peripheral arterial disease leads to reduced mobility, limited physical functioning, and poor health outcomes. Disease severity can be assessed with quantitative clinical methods and qualitative self-perceived measures of quality of life. Limited data exist to document the degree to which quantitative and qualitative measures correlate. The current study provides data on the relationship between quantitative and qualitative measures of symptomatic peripheral arterial disease. METHOD This descriptive case series was set in an academic vascular surgery unit and biomechanics laboratory. The subjects were symptomatic patients with peripheral arterial disease patients presenting with claudication. The quantitative evaluation outcome measures included measurement of ankle-brachial index, initial claudication distance, absolute claudication distance, and self-selected treadmill pace. Qualitative measurements included the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Study Short Form-36 (SF-36) Health Survey. Spearman rank correlations were performed to determine the relationship between each quantitative and qualitative measure and also between the WIQ and SF-36. RESULTS Included were 48 patients (age, 62 +/- 9.6 years; weight, 83.0 +/- 15.4 kg) with claudication (ABI, 0.50 +/- 0.20). Of the four WIQ subscales, the ankle-brachial index correlated with distance (r = 0.29) and speed (r = 0.32); and initial claudication distance and absolute claudication distance correlated with pain (r = 0.40 and 0.43, respectively), distance (r = 0.35 and 0.41, respectively), and speed (r = 0.39 and 0.39 respectively). Of the eight SF-36 subscales, no correlation was found for the ankle-brachial index, initial claudication distance correlated with Bodily Pain (r = 0.46) and Social Functioning (r = 0.30), and absolute claudication time correlated with Physical Function (r = 0.31) and Energy (r = 0.30). The results of both questionnaires showed reduced functional status in claudicating patients. CONCLUSIONS Initial and absolute claudication distances and WIQ pain, speed, and distance subscales are the measures that correlated the best with the ambulatory limitation of patients with symptomatic peripheral arterial disease. These results suggest the WIQ is the most specific questionnaire for documenting the qualitative deficits of the patient with claudication while providing strong relationships with the quantitative measures of arterial disease. Future studies of claudication patients should include both quantitative and qualitative assessments to adequately assess disease severity and functional status in peripheral arterial disease patients.

Gait variability is altered in patients with peripheral arterial disease

OBJECTIVE Claudication is the most common presentation of peripheral arterial disease (PAD), producing significant ambulatory compromise. Claudicating patients, most of whom are elderly, have reduced mobility and poor health outcomes, including an increased risk of falls. The gait of elderly fallers is characterized by increased variability. Increase in the variability of the locomotor system makes the gait more noisy and unstable. The purpose of this study is to investigate gait variability in patients with PAD. METHODS Nineteen symptomatic PAD patients (age, 63.6 +/- 9.8 years; body mass, 82.1 +/- 18.5 kg; height, 1.71 +/- 0.06 m) walked on a treadmill in the absence of pain or claudication symptoms while joint flexion and extension kinematics were captured. Results were compared with results obtained from 17 matched healthy controls (age, 65.2 +/- 12.5 years; body mass, 82.0 +/- 25.9.5 kg; height, 1.73 +/- 0.08 m). Relative joint angles were calculated for the ankle, knee, and hip flexion/extension, and the stride-to-stride variability of joint flexion and extension was calculated from at least 30 consecutive footfalls. Variability was expressed using the largest Lyapunov exponent, standard deviation, and coefficient of variation. Independent t tests were used to compare gait variability between groups. RESULTS Symptomatic PAD patients had significantly higher largest Lyapunov exponent values and coefficient of variation values for all joints, and higher standard deviation values at the ankle and the hip (P < .05). CONCLUSION Symptomatic PAD patients have increased gait variability at the ankle, knee, and hip joints at baseline ambulation in the absence of claudication pain. Our findings indicate significant baseline deterioration in the locomotor system of symptomatic PAD patients. This deterioration results in increased noise and instability of gait and is a potential contributing factor to the falls and mobility problems experienced by symptomatic PAD patients.

Peripheral arterial disease affects kinematics during walking

OBJECTIVE Claudication is the most common manifestation of peripheral arterial disease (PAD) producing significant ambulatory compromise. The purpose of this study was to use advanced biomechanical analysis to characterize the kinematic ambulatory pattern of claudicating patients. We hypothesized that compared with control subjects, claudicating patients have altered kinematic gait patterns that can be fully characterized utilizing advanced biomechanical analysis. METHODS The study examined fourteen PAD patients (age: 58 +/- 3.4 years; weight: 80.99 +/- 15.64 kg) with clinically diagnosed femoro-popliteal occlusive disease (Ankle Brachial Index (ABI): 0.56 +/- 0.03, range 0.45 to 0.65) and five healthy controls (age: 53 +/- 3.4 years; weight: 87.38 +/- 12.75 kg; ABI >or= 1). Kinematic parameters (hip, knee, and ankle joint angles in the sagittal plane) were evaluated during gait in patients before and after the onset of claudication pain and compared with healthy controls. Joint angles were calculated during stance time. Dependent variables were assessed (maximum and minimum flexion and extension angles and ranges of motion) and mean ensemble curves were generated. Time to occurrence of the discrete variables was also identified. RESULTS Significantly greater ankle plantar flexion in early stance and ankle range of motion during stance was observed in PAD patients (P < .05). Time to maximum ankle plantar flexion was shorter and time to maximum ankle dorsiflexion was longer in PAD patients (P < .05). These differences were noted when comparing PAD patients prior to and after the onset of claudication with healthy controls. The analysis of the kinematic parameters of the knee and the hip joints revealed no significant differences between PAD patients and controls. CONCLUSION PAD patients with claudication demonstrate significant gait alterations in the ankle joint that are present prior to the onset of claudication pain. In contrast, the joint motion of the hip and knee did not differ in PAD patients when compared with controls. Further research is needed to verify our findings and assess the impact of more proximal disease in PAD patients as well as the effect of revascularization on joint kinematics.

Treatment of Acute Intravascular Thrombi With Diagnostic Ultrasound and Intravenous Microbubbles

The purpose of this study was to determine whether high mechanical index (MI) impulses from diagnostic ultrasound (DUS) could dissolve intravascular thrombi using intravenous microbubbles. Using a canine model, DUS was applied during a continuous intravenous infusion of microbubbles. Completely thrombosed grafts were assigned to 2 treatment regimens: low-MI (<0.5-MI) ultrasound alone; or intermittent high-MI impulses (1.9-MI) guided by low-MI ultrasound (contrast pulse sequencing). A 20-MHz cavitation detector was placed confocal to the ultrasound transducer to make intravascular cavitation measurements in 1 dog. Intravascular cavitational activity was detected when an MI of >0.5 was applied. In grafts treated with intermittent high-MI ultrasound, angiographic success was 71% at 30 min and 79% at 45 min, compared with 20% and 30% at these times in the low-MI ultrasound alone group (p < 0.05). We conclude that a commercially available DUS transducer can successfully recanalize acute intravascular thrombi during a continuous microbubble infusion.

Transcervical Approach with Protective Flow Reversal for Carotid Angioplasty and Stenting

Purpose: To report our initial experience using a transcervical approach for carotid angioplasty/stenting (CAS) that employs internal carotid artery (ICA) flow reversal for neuroprotection. Methods: Seventeen patients (15 men; mean age 65 years, range 49–77) with significant carotid stenosis (mean 88%, 8 symptomatic) were treated with protected transcervical CAS. Eleven patients were considered at high risk for carotid endarterectomy; 8 were also considered high risk for transfemoral access (unfavorable aortic arch anatomy or advanced aortoiliac occlusive disease). Anesthesia was based on patient and anesthesiologist preferences. The approach consisted of a 2-cm cutdown over the common carotid artery and placement of a 9-F sheath. ICA flow was reversed and shunted into the jugular vein during the carotid intervention. Results: Access and carotid stenting were successful in all cases. Thirteen procedures were performed under general and 4 under local anesthesia. Mean flow reversal time was 34±4 minutes (25 minutes in the last 7 cases). The patients tolerated the procedure well and had no neurological events. Four (23%) patients had significant oozing from the operative site; 2 developed small neck hematomas that were treated conservatively. All patients were discharged on the first postoperative day. There were no deaths, changes in neurological status, or restenosis over a mean follow-up of 12 months (range 1–24). Conclusions: Our initial experience demonstrates that a transcervical approach is a viable alternative for CAS. The procedure can be performed safely, with good initial clinical outcomes. The approach allows carotid flow reversal and emboli protection without introducing neuroprotection devices. The method appears best suited for patients at high risk for endarterectomy and transfemoral access.

Oxidative damage and myofiber degeneration in the gastrocnemius of patients with peripheral arterial disease

Peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in arteries supplying the legs, affects an estimated 27 million people in Europe and North America. Increased production of reactive oxygen species by dysfunctional mitochondria in leg muscles of PAD patients is viewed as a key mechanism of initiation and progression of the disease. Previous studies demonstrated increased oxidative damage in homogenates of biopsy specimens from PAD gastrocnemius compared to controls, but did not address myofiber-specific damage. In this study, we investigated oxidative damage to myofibers as a possible cause of the myopathy of PAD. To achieve this, we developed and validated fluorescence microscopy procedures for quantitative analysis of carbonyl groups and 4-hydroxy-2-nonenal (HNE) adducts in myofibers of biopsy specimens from human gastrocnemius. PAD and control specimens were evaluated for differences in 1) myofiber content of these two forms of oxidative damage and 2) myofiber cross-sectional area. Furthermore, oxidative damage to PAD myofibers was tested for associations with clinical stage of disease, degree of ischemia in the affected leg, and myofiber cross-sectional area. Carbonyl groups and HNE adducts were increased 30% (p < 0.0001) and 40% (p < 0.0001), respectively, in the myofibers of PAD (N = 34) compared to control (N = 21) patients. Mean cross-sectional area of PAD myofibers was reduced 29.3% compared to controls (p < 0.0003). Both forms of oxidative damage increased with clinical stage of disease, blood flow limitation in the ischemic leg, and reduced myofiber cross-sectional area. The data establish oxidative damage to myofibers as a possible cause of PAD myopathy.

Bilateral claudication results in alterations in the gait biomechanics at the hip and ankle joints.

Claudication is the most common symptomatic manifestation of peripheral arterial disease (PAD), producing significant ambulatory compromise. The purpose of this study was to use advanced biomechanical gait analysis to determine the gait alterations occurring in claudicating patients both before and after onset of claudication pain in their legs. Hip, knee, and ankle joint moments were measured in claudicating patients (age: 64.46+/-8.47 years; body mass: 80.70+/-12.64kg; body height: 1.72+/-0.08m) and were compared to gender-age-body mass-height-matched healthy controls (age 66.27+/-9.22 years; body mass: 77.89+/-10.65kg; body height: 1.74+/-0.08m). The claudicating patients were evaluated both before (pain-free (PF) condition) and after (pain condition) onset of claudication pain in their legs. Thirteen symptomatic PAD patients (26 claudicating limbs) with bilateral intermittent claudication (IC) and 11 healthy controls (22 control limbs) were tested during level walking at their self-selected speed. Compared to controls, PAD hip and ankle joints demonstrated significant angular kinematics and net internal moment changes. Alterations were present both in PF and pain conditions with several of them becoming worse in the pain condition. Both PF and pain conditions resulted in significantly reduced peak hip extensor moment (5.62+/-1.40 and 5.63+/-1.33% BWxBH, respectively) during early stance as compared to controls (7.53+/-1.16% BWxBH). In the pain condition, PAD patients had a significantly reduced ankle plantar flexor moment (7.56+/-1.41% BWxBH) during late stance as compared to controls (8.65+/-1.27% BWxBH). Furthermore, when comparing PF to pain conditions, there was a decreased peak plantar flexor moment (PF condition: 8.23+/-1.37 vs. pain condition: 7.56+/-1.41% BWxBH) during late stance. The findings point to a weakness in the posterior compartment muscles of the hip and calf as being the key factor underlying the PAD gait adaptations. Our findings establish a detailed baseline description of the changes present in PAD patients joint angles and moments during walking. Since IC is primarily a gait disability, better understanding of the abnormalities in joint and muscle function will enhance our understanding of the gait impairment and may lead to novel, gait-specific treatments.