Skip Navigation LinksHome > April 2014 - Volume 26 - Issue 2 > Effect of Mild Hypothermic Cardiopulmonary Bypass on the Amp...
Journal of Neurosurgical Anesthesiology:
doi: 10.1097/ANA.0000000000000016
Clinical Investigation

Effect of Mild Hypothermic Cardiopulmonary Bypass on the Amplitude of Somatosensory-evoked Potentials

Zanatta, Paolo MD*; Bosco, Enrico MD*; Comin, Alessandra PhD; Mazzarolo, Anna Paola MS; Di Pasquale, Piero MD; Forti, Alessandro MD*; Longatti, Pierluigi MD§; Polesel, Elvio MD; Stecker, Mark MD, PhD; Sorbara, Carlo MD*

Free Access
Article Outline
Collapse Box

Author Information

*Department of Anesthesia and Intensive Care

Neuromonitoring Project, Department of Anesthesia and Intensive Care

Departement of Cardiovascular Disease

§Department of Neurosurgery, Treviso Regional Hospital, University of Padova, Padova

Department of Anesthesia and Intensive Care, Rovigo Regional Hospital, Rovigo, Italy

Department of Neuroscience, Winthrop University Hospital, NY

This work was conducted at the Department of Anesthesia and Intensive Care and Cardiovascular Diseases of Treviso Regional Hospital, Italy.

Funding for this study was provided by Regione Veneto, Italy, for a project on the reduction of neurodysfunction after cardiac surgery and neurosurgery and improvement in multimodality neuromonitoring for neurophysiological technicians and psychologists. This study was also carried out with a grant by the Veneto Banca Foundation of Treviso for a psychologist.

The authors have no conflicts of interest to disclose.

Reprints: Paolo Zanatta, MD, Department of Anesthesia and Intensive Care, Treviso Regional Hospital, Azienda Ospedaliera Ulss 9, Piazzale Ospedale 1, Treviso 31100, Italy (e-mail:

Received April 22, 2013

Accepted August 26, 2013

Collapse Box



Several neurophysiological techniques are used to intraoperatively assess cerebral functioning during surgery and intensive care, but the introduction of hypothermia as a means of intraoperative neuroprotection has brought their reliability into question. The present study aimed to evaluate the effect of mild hypothermia on somatosensory-evoked potentials’ (SSEPs) amplitude and latency in a cohort of cardiopulmonary bypass (CPB) patients as the temperature reached the steady-state.

Materials and Methods:

The amplitude and latency of 4 different SSEP signals—N9, N13, P14/N18 interpeak, and N20/P25—were evaluated retrospectively in 84 patients undergoing CPB during normothermic (36°C±0.43°C) and mild hypothermic (32°C±1.38°C) conditions. SSEPs were recorded in normothermia immediately after the induction of anesthesia and in hypothermia as the temperature reached its steady-state, specifically, when the nasopharyngeal temperature was equivalent to the rectal temperature (±0.5°C). A paired-samples t test was performed for each SSEP to test the differences in latencies and amplitudes between normothermic and hypothermic conditions.


Compared with normothermia, hypothermia not only significantly increased the latency of all SSEPs, N9 (P<0.001), N13 (P<0.001), P14/N18 (P<0.001), and N20/P25 (P<0.001), but also the amplitude of N9 (P<0.001) and N20/P25 (P<0.001).


The increased amplitude in particularly of cortical SSEPs (N20/P25), detected specifically during steady-state hypothermia, seems to support the clinical utility of this methodology in monitoring the brain function not only during cardiac surgery with CPB, but also in other settings like therapeutic hypothermia procedures in an intensive care unit.

Hypothermia has proved to be a successful strategy in limiting the neurological damage associated with cardiac surgery, creating a condition that protects neural tissue and leads to a reduced cerebral metabolic rate; decreased excitotoxic neurotransmitter release; changed ion homeostasis, acid-base balance, calcium flux, membrane lipid peroxidation, free radical reactions, permeability of the blood-brain barrier; and alterated arachidonic acid cascade.1

Multimodal brain monitoring seems to provide the opportunity to warn against the impending injury to the nervous system and to change the intraoperative strategy before the appearance of permanent damage.2,3 This can be done using techniques evaluating brain metabolism (ie, near-infrared spectroscopy and oxygen venous saturation from a jugular bulb), hemodynamics (ie, transcranial Doppler), and functioning (ie, electroencephalography [EEG] and somatosensory-evoked potentials [SSEPs]). Among others, as SSEP monitors the integrity of the somatosensory pathway and in particular the somatosensory cortex, its value in the detection of intraoperative stroke seems to be crucial.4,5

Although multimodal brain monitoring during cardiac operations is not yet routine, EEG and SSEP monitoring is frequently performed in clinical practice and its utility has been advocated during cardiac surgery with hypothermic cardiopulmonary bypass (CPB).3 In the last few years, several studies have investigated the effects of hypothermia on the EEG and SSEP signals, both in animal models and humans. Results agreed in identifying the sensitivity of both spontaneous (EEG) and evoked (SSEPs) neural responses to changes in temperature, but if the slowdown of EEG signals as the temperature decreased was a common finding, the response of SSEPs to temperature was not so standardized. In fact, despite the general increase in SSEPs’ latency as the temperature dropped, data regarding their amplitude was highly conflicting for mild temperature reductions. Studies performed in humans during hypothermic CPB reported a general slight decrease in SSEPs’ amplitude when data were collected during cooling.6–11 The only exception from the previous literature was described by Russ et al,12 who, nonetheless, observed a nonsignificant increase in SSEPs’ amplitude during CPB. Conversely, studies performed during hypothermia, but in conditions of spontaneous circulation, reported an increase in SSEPs’ amplitude in both humans and animals.13–15 Only Kottenberg-Assenmacher et al16 did not find evidence that hypothermia affects SSEPs’ amplitude.

The present study aimed to compare the values of SSEPs’ latency and amplitude during mild hypothermic CPB to those in normothermic conditions. However, in this study, differently from previous studies, data were collected only when the temperature reached the steady-state.

Back to Top | Article Outline



Eighty-four patients undergoing elective cardiac surgery with mild hypothermic CPB were recruited for the present study. These patients, who experienced stable anesthetic conditions and no neurological complications, belonged to a more extended group of 166 patients who underwent intraoperative neurophysiological monitoring during cardiac surgery with nonpulsatile cardiopulmonary bypass from July 2007 to July 2010.3 Patients experiencing a total intravenous anesthesia whose body temperature information was recorded in the neurophysiological report were selected. Our casuistry excluded pediatric cardiac surgery. Approval for a retrospective data analysis was obtained from our Institutional Review Board. Written informed consent for multimodal brain monitoring was obtained from all patients.

Back to Top | Article Outline
General Procedures

All patients were premedicated with 1 μg/kg of fentanyl and 0.05 mg/kg of midazolam, administered intravenously. The induction of anesthesia was established with 3 to 5 μg/kg of fentanyl, 2 mg/kg of propofol, and 0.6 mg/kg of rocuronium bromide. Afterward, anesthesia was maintained using propofol 3 to 6 mg/kg/h and remifentanil 0.3 to 0.4 μg/kg/h or propofol 3 to 6 mg/kg/h and sufentanil 0.1 to 0.3 μg/kg/h in the doses needed to maintain bispectral index signals values of <40. An α-stat hypothermic CPB procedure with a nonpulsatile flow rate of 2.4 L/min/m2 was used. Heparin was administrated in a blood dosage calculated by the hemostatic management system (HMS, Medtronics Inc. Minneapolis, MN).

Back to Top | Article Outline

The SSEP technique used has been previously described.5 Four channels for each side of stimulation were used (Fig. 1): 1: Fpz-C4′/C3′ detected the N20/P25 cortical potential; 2: right Erb’s point/left Erb’s point-C4′/C3′ detected the interpeak between P14 and N18 subcortical potential (referred to P14/N18 in the text); 3: Fpz-CV detected the N13 cervical potential; 4: Fpz-right Erb’s point/left Erb’s point detected the N9 brachial plexus potential. Erb’s point needles were placed 3 cm posteriorly on the supraclavicular fossa to avoid any interference with subclavian vein cannulation. The spinal electrode CV was placed over the fifth cervical spinous process. Central conduction time (CCT), defined as the conduction time between the brainstem and the cortex, was calculated as the difference between the latencies of N20 and N13. The latency was measured as the time elapsed between stimulation and the peak of interest (N20, P14, N13, and N9). The amplitude of N20 was measured as the difference between the peaks of N20 and P25. As P14 and N18 are 2 distinct evoked potentials that reflect respectively the bulbar and the thalamus-cortical generator, we arbitrarily assumed the interpeak P14/N18 as a subcortical potentials. The amplitude of N13 and N9 was measured as the difference between their peaks and the baseline.

Image Tools

SSEP recording parameters were 30 Hz for low-frequency filter and 350 Hz for high-frequency filter with an analysis time of 100 milliseconds and 50 sweeps for every curve averaged; the stimulus duration was 200 milliseconds; the stimulus frequency was 3.3 Hz with an intensity of 10 mAmp. These recording parameters allowed reproducible traces in 20 seconds. Electrical stimulation was performed using needle electrodes placed on both the wrists near the median nerve; to reduce the time response to a possible monolateral or bilateral brain ischemia we routinely provided the simultaneous nerve stimulation as suggested for intraoperative neuromonitoring.5 The ground electrode was placed on the left shoulder. Electrode impedance was kept below 1 kΩ. SSEPs were recorded using an Eclipse Neurological Workstation-Axon System (AXON Systems Inc., New York, NY).

SSEPs were recorded at 2 different points. (1) In normothermia (36°C±0.43°C), after the induction of anesthesia before the skin incision. (2) At the temperature steady-state (32°C±1.38°C) for hypothermia, during CPB. Temperature was measured at the nasopharyngeal site and, as a control, rectally. Temperature was considered at the steady-state when the nasopharyngeal and rectal values were similar (±0.5°C). The time required for balancing the 2 temperatures took approximately 15 minutes and depended on multifactorial reasons such as the body surface area, the gradient, the speed of cooling, and the peripheral vascular resistance.

Back to Top | Article Outline
Statistical Analysis

To test differences in the latency and amplitude of N9, N13, P14/N18, and N20/P25 in normothermic and hypothermic conditions, a paired-samples t test was performed for each SSEP; each SSEP amplitude and latency was considered as the average between the left and right potential. Cohen d was reported as the effect size measure. The statistical analyses were performed using the SPSS statistical software package (Version 19.0, SPSS Inc., Chicago, IL). P values <0.01 were considered to be statistically significant.

Back to Top | Article Outline


Analysis of SSEPs’ Amplitude

There was a significant increase of the amplitude of N9 (t(73)=−5.6, P<0.001, d=−0.5) and N20/P25 (t(83)=−6.6, P<0.001, d=−0.5) from normothermia to hypothermia. On the contrary, the amplitudes of P14/N18 (t(70)=−1.2, P=0.05, d=−0.1) and N13 (t(67)=−2.0, P=0.01, d=−0.2) did not change significantly (Table 1 and Fig. 2).

Image Tools
Image Tools
Back to Top | Article Outline
Analysis of SSEPs’ Latency

There were significant differences between normothermia and hypothermia concerning the latency of all the SSEPs considered: N9 (t(75)=−9.1, P<0.001, d=−0.7), N13 (t(72)=−10.3, P<0.001, d=−0.9), P14/N18 (t(74)=−11.3, P<0.001, d=−1.2), and N20/P25 (t(83)=−18.9, P<0.001, d=−1.8). Higher values were recorded in hypothermia compared with normothermia. CCT increased by 31% (t(72)=−12.5, P<0.001, d=−4.8) (Table 2 and Fig. 3).

Image Tools
Image Tools
Back to Top | Article Outline


According to our knowledge, this is the first study demonstrating an increase in the amplitude and latency of all SSEPs during mild hypothermic cardiopulmonary bypass evaluated in a steady-state temperature condition (Fig. 4). These data are in contrast to what has been reported in previous literature regarding SSEPs’ amplitude being lower during cooling than during basal normothermic value. In the present study, we evaluated both peripheral and cortical SSEPs in patients undergoing cardiac surgery assisted by CPB in mild hypothermic conditions during stable total intravenous anesthesia19–21 and systemic perfusion pressure. We measured the amplitude of SSEPs related to the brachial plexus, Erb point, (N9), lower cervical spine (N13), brainstem-thalamic junction (the interpeak between P14 and N18), and primary somatosensory cortex (N20/P25) (Fig. 1). We verified that when the temperature remained steady at around 32°C, both the amplitude and the latency of all SSEPs increased (Fig. 4). Although the N13 and P14 amplitudes did increase, their variation was not statistically significant. We attributed such a result to 2 distinct factors. First, subcortical potentials generally have lower signal to noise levels than cortical potentials. Second, there are a number of overlapping waves in the region of N13 (eg, N11) whose configuration likely changes with temperature. The changes in SSEP wave latency and CCT were in general agreement with those in previous literature, even though the temperature-related changes in SSEP latency were lower than those reported by others,6–11 ranging from 8% for N9 to 17% for N20, probably because in these studies data were collected during cooling.

Image Tools

Some previous studies7,8 reported increases during cooling in the amplitude of the ERB’s point potential, but not in N20/P25. As the ERB’s point potential (N9) is strongly related to the nerve action potential produced stimulating the wrist, it is supposed to respond to temperature as other nerve action potentials do. The increase in the nerve action potential’s amplitude in mild hypothermic conditions has been widely acknowledged by neurophysiologists for a long time.22,23 Recently, Stecker and colleagues24,25 provided further experimental support to our findings, stating that in a rat sciatic nerve preparation, the amplitude of the nerve action potential increased as temperature was reduced to 27°C, decreased as temperature dropped from 26°C to 16°C, and, finally, disappeared permanently only after cooling below 10°C for extended periods. There are 2 mechanisms that could explain the increase in amplitude of the Erb’s point potential at mild hypothermia. First, in mild hypothermia, the reduced activity of the energy-generating systems may allow a slight depolarization of the nerve membrane that could increase its excitability and hence increase synchronized firing in axons. Second, the inactivation of sodium channels may exhibit slower kinetics at lower temperatures thus prolonging the duration of action potentials and increasing the amplitude of the nerve action potential recorded from many fibers. The further decline in amplitude reported both by Stecker and colleagues24,25 in the range 27°C to 16°C could be attributed to an increasing failure of axons to fire action potentials during severe membrane depolarization. It could also be attributed to changes in the passive properties of the nerve membrane.

Synaptic mechanisms26–28 may also be involved in the changes concerning N20/P22. Among others, the reduced activity of neurotransmitter catabolism could increase the amount of neurotransmitter available to activate receptors29 and therefore increase the chance of a vesicle to be released in response to an action potential.30

The increased amplitude of the N20/P25 cortical potential recorded in this study and the lower amplitudes seen in the previous studies during hypothermia can likely be attributed to the fact that, in this study, all data were obtained at a stable temperature, whereas in the other studies the data were taken during cooling. The effect of cooling results in the overlap of various N20/P25 waveforms of differing latency and amplitude during the averaging process. As the N20/P25 is a biphasic potential, whereas the N9 potential is not, a partial cancellation and subsequent reduction in amplitude would likely be seen.

Understanding amplitude changes is critical for effective neurophysiological monitoring as such changes in cortical potentials are the main indicators of brain hypoperfusion and stroke during cardiac surgery.4,31

Our results agreed with the previous study of Lang et al14 and Russ et al,12 where the effect of hypothermia on the amplitude of SSEP seemed not to be dependent on the type of circulation (ie, spontaneous vs. extracorporeal) but on the rate of cooling and the temperature reached.

We recognize some limits in our study. First, it could be objected that recording SSEP before and during CPB could not be the appropriate methodological approach; nevertheless, we could not exclude such a limit given the retrospective design of our study. Second, we admit the need of considering the effect of laterality in simultaneous nerve stimulation during hypothermia to strengthen our neurophysiological comprehension of the whole set of data SSEP monitoring could give. Finally, we did not have the chance to include SSEP data during cooling because reaching the steady-state at every degree of cooling would increase the length of the surgical procedure; moreover only temperatures at the beginning of surgery and during stable hypothermia were recorded. As a result, further studies will be conducted to fill in the gaps. Nevertheless, our data provide useful information to a correct interpretation of SSEPs during cardiac surgery and enhances the potential clinical impact of evoked potentials in cerebral monitoring both during surgery and in critical care units where hypothermia is used to treat postanoxic-ischemic comatosed patients.17,18 Indeed, in this last clinical scenario, the use of mild hypothermia has undermined the validity of classic bedside neurological examinations (ie, brainstem reflexes, motor response, myoclonus status epilepticus, EEG, and biochemical markers of cerebral injury18). Our data support the increasing evidence that the absence of N20/P25 in hypothermia could be considered a reliable prognostic indicator as in normothermic patients.32–34 In fact, during accidental hypothermia, the disappearance of consciousness begins at temperatures <27°C to 28°C35,36 supporting a more complementary role of SSEP versus EEG37 in exploring brain function and the prognosis of coma during mild hypothermia.

In conclusion, we showed that during cardiac surgery assisted by CPB, SSEPs’ latencies (N9, N13, P14, N20, and CCT) and amplitudes (N9, N13 and N20/P25) increased when the temperature remained steady at mild hypothermic conditions. We suppose that our results differ from previous studies because we recorded SSEP values at the steady-state instead of during rapid deep cooling. In our opinion our findings encourage a more extended application of SSEP monitoring in evaluating cerebral functioning, especially in critical conditions such as during surgery and in critical care units.

Back to Top | Article Outline


1. Gravlee GP, Davis RF, Kurusz M, et al .Cardiopulmonary Bypass: Principles and Practice. 2000; :2nd ed.Philadelphia:Lippincott Williams & Wilkins Publishers.

2. Edmonds HL .Standard of care for central nervous system monitoring during cardiac surgery.J Cardiothorac Vasc Anesth. 2010; 24:541–543.

3. Zanatta P, Messerotti Benvenuti S, Bosco E, et al .Multimodal brain monitoring reduces major neurologic complications in cardiac surgery.J Cardiothorac Vasc Anesth. 2011; 25:1076–1085.

4. Stecker MM, Cheung AT, Patterson T, et al .Detection of stroke during cardiac operations with somatosensory-evoked responses.J Thorac Cardiovasc Surg. 1996; 112:962–972.

5. Florence G, Guerit JM, Gueguen B .Electroencephalography (EEG) and somatosensory-evoked potentials (SEP) to prevent cerebral ischemia in the operating room.Clin Neurophysiol. 2004; 34:17–32.

6. Markand ON, Warren CH, Moorthy SS, et al .Monitoring of multimodality-evoked potentials during open heart surgery under hypothermia.Electroencephalogr Clin Neurophysiol. 1984; 59:432–440.

7. Van Rheineck Leyssius AT, Kalkman CJ, et al .Influence of moderate hypothermia on posterior tibial nerve somatosensory-evoked potentials.Anesth Analg. 1986; 65:475–480.

8. Sebel PS, de Bruijn NP, Neville WK .Effect of hypothermia on median nerve somatosensory-evoked potentials.J Cardiothorac Anesth. 1988; 2:326–329.

9. Markand ON, Warren C, Mallik GS, et al .Effects of hypothermia on short latency somatosensory evoked potentials in humans.Electroencephalogr Clin Neurophysiol. 1990; 77:416–424.

10. Porkkala T, Kaukinen S, Häkkinen V, et al .Effects of hypothermia and sternal retractors on median nerve somatosensory-evoked potentials.Acta Anaesthesiol Scand. 1997; 41:843–848.

11. Kochs E .Electrophysiological monitoring and mild hypothermia.J Neurosurg Anesthesiol. 1995; 7:222–228.

12. Russ W, Sticher J, Scheld H, et al .Effects of hypothermia on somatosensory-evoked responses in man.Br J Anaesth. 1987; 59:1484–1491.

13. Browning JL, Heizer ML, Baskin DS .Variations in corticomotor and somatosensory-evoked potentials: effects of temperature, halothane anesthesia, and arterial partial pressure of CO2. Anesth Analg. 1992; 74:643–648.

14. Lang M, Welte M, Syben R, et al .Effects of hypothermia on median nerve somatosensory-evoked potentials during spontaneous circulation.J Neurosurg Anesthesiol. 2002; 14:141–145.

15. Madhok J, Wu D, Xiong W, et al .Hypothermia amplifies somatosensory-evoked potentials in uninjured rats.J Neurosurg Anesthesiol. 2012; 24:197–202.

16. Kottenberg-Assenmacher E, Armbruster W, Bornfeld N, et al .Hypothermia does not alter somatosensory-evoked potential amplitude and global cerebral oxygen extraction during marked sodium nitroprusside-induced arterial hypotension.Anesthesiology. 2003; 98:1112–1118.

17. Freye E .Cerebral monitoring in the operating room and the intensive care unit—an introductory for the clinician and a guide for the novice wanting to open a window to the brain. Part II: sensory-evoked potentials (SSEP, AEP, VEP).J Clin Monit Comput. 2005; 19:77–168.

18. Samaniego EA, Persoon S, Wijman CA .Prognosis after cardiac arrest and hypothermia: a new paradigm.Curr Neurol Neurosci Rep. 2011; 11:111–119.

19. Deiner S .Highlights of anesthetic considerations for intraoperative neuromonitoring.Semin Cardiothorac Vasc Anesth. 2010; 14:51–53.

20. Ravussin P, de Tribolet N, Wilder-Smith OH .Total intravenous anesthesia is best for neurological surgery.J Neurosurg Anesthesiol. 1994; 6:285–289.

21. Jameson LC, Sloan TB .Neurophysiologic monitoring in neurosurgery.Anesthesiol Clin. 2012; 30:311–331.

22. Delbeke J, Kopec J, McComas AJ .Effects of age, temperature, and disease on the refractoriness of human nerve and muscle.J Neurol Neurosurg Psychiatry. 1978; 41:65–71.

23. Denys EH .AAEM minimonograph #14. The influence of temperature in clinical neurophysiology.Muscle Nerve. 1991; 14:795–811.

24. Stecker MM, Baylor K .Peripheral nerve at extreme low temperatures 1: effects of temperature on the action potential.Cryobiology. 2009; 59:1–11.

25. Baylor K, Stecker MM .Peripheral nerve at extreme low temperatures 2: pharmacologic modulation of temperature effects.Cryobiology. 2009; 59:12–18.

26. Ricker K, Hertel G, Stodieck S .The influence of local cooling on neuromuscular transmission in the myasthenic syndrome of Eaton and Lambert.J Neurol. 1977; 217:95–102.

27. Adams BA .Temperature and synaptic efficacy in frog skeletal muscle.J Physiol. 1989; 408:443–455.

28. Sohmer H, Gold S, Cahani M .Effects of hypothermia on auditory brain-stem and somatosensory-evoked responses. A model of a synaptic and axonal lesion.Electroencephalogr Clin Neurophysiol. 1989; 74:50–57.

29. Foldes FF, Kuze S, Vizi ES .The influence of temperature on neuromuscular performance.J Neural Transm. 1978; 43:27–45.

30. Hubbard JI, Jones SF, Landau EM .The effect of temperature change upon transmitter release, facilitation and post-tetanic potentiation.J Physiol. 1971; 216:591–609.

31. Cheung AT, Savino JS, Weiss SJ, et al .Detection of acute embolic stroke during mitral valve replacement using somatosensory-evoked potential monitoring.Anesthesiology. 1995; 83:208–210.

32. Tiainen M, Kovala TT, Takkunen OS, et al .Somatosensory and brainstem auditory-evoked potentials in cardiac arrest patients treated with hypothermia.Crit Care Med. 2005; 33:1736–1740.

33. Bouwes A, Binnekade JM, Kuiper MA .Prognosis of coma after therapeutic hypothermia: a prospective cohort study.Ann Neurol. 2012; 71:206–212.

34. Grippo A, Carrai R, Fossi S, et al .Absent SEP during therapeutic hypothermia did not reappear after re-warming in comatose patients following cardiac arrest.Minerva Anestesiol. 2013; 79:360–369.

35. Durrer B, Brugger H, Syme D .International Commission for Mountain Emergency Medicine: the medical on-site treatment of hypothermia: ICAR-MEDCOM recommendation.High Alt Med Biol. 2003; 4:99–103.

36. Danzl DF. Auerbach P .Accidental hypothermia.Wilderness Medicine. 2007; .St. Louis:Mosby; 125–160.

37. Cloostermans MC, van Meulen FB, Eertman CJ, et al .Continuous electroencephalography monitoring for early prediction of neurological outcome in postanoxic patients after cardiac arrest: a prospective cohort study.Crit Care Me. 2012; 40:2867–2875.


therapeutic hypothermia; somatosensory-evoked potentials; cardiopulmonary bypass

Copyright © 2014 by Lippincott Williams & Wilkins


Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.