Managing complex patients in a dynamic perioperative environment is the focus of my clinical efforts, teaching and research. I spend the majority of my time in cardiovascular anesthesia care and clinical teaching, with time specifically devoted to research and didactic teaching. Increasing number of complex surgery are being done in high-risk patients. Improving their perioperative outcomes is a challenge due to the lack of patient specific outcome data, and reliable and readily obtainable risk stratification methods specifically in high-risk groups. My outcomes research work started with managing high-risk patients combined with didactics in All India Institute Medical Sciences (Top federally funded medical school in India) and Harvard Medical School (BIDMC anesthesia department). Working in three different continents (India, United Kingdom and US) has shown me that in order to improve patient’s outcome, continuing clinical activity is necessary to understand the challenges of the entire pre-, intra- and postoperative period along with the provider (surgeons, anesthesiologists and nurses) variability in clinical care. My initial research work was focused on the common problems that led to readmissions following surgery: acute postoperative pain, nausea and vomiting, bleeding, major adverse cardiac and pulmonary events.
The concept of central sensitization for pain established in 1990s paved way for using preemptive analgesia to tackle acute postoperative pain following major cardiothoracic surgery. I used morphine and ketamine as epidural analgesics to provide preemptive analgesia in thoracic surgery patients. These were ideal drugs in a resource constraint environment. This post-grad thesis work still remains as one of eight randomized studies using epidural technique for preemptive analgesia (Anaesth Intensive Care 2000). My other investigations on preemptive analgesia led to several key publications and taught me that there is a sustained secondary injury over 48 hours following major surgery, which helped me conduct a successful work using intravenous acetaminophen (JAMA 2019). Preemptive concept evolved into multimodal analgesia, which is a well-established technique in current postoperative pain management strategies.
I then focused on the prevention of resistant postoperative pain. In a prospective, randomized, double-blinded trial, we evaluated the safety and efficacy of epidural ketamine combined with morphine (J Clin Anesth 2001; Anesth Analg 2001). The often-cited first ketamine metaanalysis (Anesth Analg 2004) not only showed the opioid sparing benefits but also its effectiveness in resistant postoperative pain from the NMDA receptor antagonism. This work led to several ketamine studies worldwide. Intravenous ketamine is now an established method to treat resistant postoperative pain. I realized then the importance of research during residency. That led me to establish residency research curriculum at BIDMC in 2014 and ACGME approved Loring residency research track in 2018. Having a critical mass of academic anesthesiologists is essential for the profession. This decade long acute postoperative pain work led to widespread recognition amongst my peers. I wrote the editorial for a seminal metanalysis on epidural analgesia in the Annals of Surgery (2014). I was/am determined to change the current sub-optimal pain management strategy following cardiac surgery that exists worldwide.
I started exploring ultrasound guided regional blocks, prehabilitation with meditation, and other non-opioid strategies for pain management in cardiac surgical patients. Scheduled prophylactic Intravenous acetaminophen for 48 hours was piloted (F1000 research in 2017, 1445 views, 520 downloads, https://f1000research.com/articles/6-1842/v2) followed by the actual trial that effectively reduced postoperative delirium in older cardiac surgical patients (JAMA 2019, altmetric score of 235, top 5% of all research, https://jamanetwork.altmetric.com/details/55766174), and has been referred by multiple news agencies and quoted as ground breaking research. Subsequent multicenter study proposal that focuses on the prevention of postoperative pain and delirium scored a third percentile and has been funded by the National Institute of Ageing (pandoraclinicaltrial.org). Further work with prehabilitation and sternal block should help build a postoperative pain bundle and spare opioid use.
I have always focused on reducing the major adverse cardiac and pulmonary events following high-risk surgery. This is illustrated by a) the epidemiology of vascular amputation (Anesth Analg 2005), b) moderate glycemic control in vascular surgery, and c) use of technology (echocardiography, signal processing and development of prototypes). I demonstrated that moderate glucose control reduced postoperative myocardial ischemia with less hypoglycemic events for these patients (Anesthesiology 2009 with an accompanying editorial). It is important to note that the concept of moderate glycemic control was done even before the seminal work (NICE study, 2012) was conceptualized and published. I then showed the association between glycemic variability and postoperative adverse events following cardiac surgery (Anesth Analg 2014, 2017).
My work also emphasized prediction of adverse events following complex surgery. I am developing a novel prototype for non-invasive, echo-guided central oximetry funded by CIMIT in collaboration with the MGH Wellman Optics Lab (2012). My R01 work, "Dynamic markers of intraoperative instability," in collaboration with the Rey Institute for Nonlinear Dynamics in Medicine explored risk stratification with novel nonlinear measures (Fragmentation and Multiscale Entropy, Journal of Clinical Monitoring and Computing 2019, Anesthesia and Analgesia 2019). Preoperative blood pressure entropy can be obtained with a continuous noninvasive blood pressure monitor and is being currently explored as a potential preoperative noninvasive monitor to ascertain risk in the surgeon’s office.
In parallel, a dozen of my peer-reviewed papers have incorporated perioperative transesophageal echocardiography (TEE). I have led the dissemination TEE to promote patient safety in developing regions of the world. I founded a national course in India in 2007 (http://teepgi.org/node/3), and anesthesiologists from Harvard, Mayo Clinic, University of Pittsburgh, Cleveland Clinic, and Canada now participate in this annual event. This course broke the hierarchy and made TEE available for all practitioners with the establishment of a formal national TEE board certification in India. I also co-founded an anesthesia update bringing together faculties of Harvard and the premier All India Institute of Medical Sciences. I have written a textbook on problem-based echocardiography and invited editorials on TEE (Anesthesiology 2010, Ann Card Anaesth 2011, 2014).
My background in clinical effectiveness research (MPH) from the Harvard School of Public Health (2009) has immensely benefited my research endeavors. I edited textbooks in the fields of dynamic measurement of fluid responsiveness (2010) and perioperative care of the aortic surgery (2011; chapters downloaded 50000 times and top 25% of most downloaded ebooks). I take special pride in inspiring residents and colleagues to become clinician scientists. I chaired our Resident Research Committee, directed Journal Clubs, taught numerous lectures and CME courses locally, nationally and internationally, and mentor others. These educational activities permeate and unify all of my clinical and research endeavors.
Another important and often ignored area has been providers’ wellbeing. We have shown that about a third of perioperative providers are stressed and doing a one-time short 15 minute practice removed their negativity. I have organized (Harvard Sanders theater, https://www.youtube.com/watch?v=w7irEcQHChw, 2.3 million views) and done numerous presentations to increase awareness with an evidence based approach. I believe that providing online or web based short practices that can be self learnt and followed is better than a one size fit all approach. Our parallel work with behavioral questionnaires, endocannabinoids, BDNF, EEG and functional MRI are showing further evidence to the positive changes seen in the perioperative provider (manuscripts in process). In summary, I have a demonstrated record of successful and productive teaching, clinical and research work in the field of perioperative medicine that incorporates preoperative, intraoperative and postoperative strategies combined with provider wellbeing (https://projects.iq.harvard.edu/subramaniamresearchlab/ ).